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CHAPTER 24: GENETICS AND GENOMICS
OBJECTIVES:
1. Define the term genetics.
2. Distinguish between a gene and a chromosome, and state how many of each humans possess.
3. State what the abbreviation DNA stands for and give the function(s) of this macromolecule.
4. Explain the following process: DNA (gene) ---> messenger RNA —>Protein
5. List several functions that proteins serve and state which proteins are the most important.
6. Define the term mutation and discuss at least three results that may occur due to a mutation.
7. Explain what is meant by the term sexual reproduction.
8. Distinguish between gametes and somatic cells in terms of their genetic makeup.
9. Name the cell that results from fertilization of gametes and give its genetic makeup.
10. Define the term meiosis and explain its significance.
11. Explain what is represented in a human karyotype.
12. Define the term homologous chromosomes, and explain what happens between homologous chromosomes during Prophase I of meiosis.
13. Distinguish between autosomes and sex chromosomes, and state how many pairs of each humans possess.
14. Define the term allele, and give an example that illustrates the distinction between a gene and an allele.
15. Distinguish between a dominant and recessive allele of a gene pair and give an example of each.
16. State the genetic makeup of an individual who is homozygous for a trait versus one who is heterozygous for a trait, both in words and using typical letters.
17. Explain the difference between the genotype and phenotype of a trait.
18. Illustrate a Punnett square and explain why it is used.
19. Given a similar problem to those below, be able to express the results both genotypically and phenotypically:
a. Brown eyes are dominant over blue eyes. If an individual who is homozygous dominant for eye color is crossed with a blue-eyed individual, what are the expected results of their offspring?b. Widow’s peak is dominant over straight hairline. If an individual who is heterozygous for hairline is crossed with an individual with a straight hairline, what are the expected results of their offspring?
20. List the three major modes of inheritance and name a disease that results from each.
21. Given a similar problem to those below, be able to express the results both genotypically and phenotypically:
a. Cystic fibrosis follows autosomal recessive inheritance. If parents have a child afflicted with CF, what are the chances that their next child will be afflicted with the disease?b. Huntington’s Disease follows autosomal dominant inheritance. If a normal individual and a person carrying the HD allele become pregnant, what are the chances that this child will be afflicted with the disease?
22. Explain how sex is determined in humans.
23. Discuss the characteristics of sex-linked traits and name a disease that is transmitted in this fashion.
24. Define the term aneuploidy, explain how it may occur, and name the most common condition that results from aneuploidy in humans.
25. Define the term genomics and name the key difference between genomics and genetics.
26. Name the tests that can be performed prenatally to determine many genetic disorders.
27. Explain why genetic counseling would be useful for some couples.
28. Define the term gene therapy and discuss its significance in treating human disease.
29. Define and compare the terms:incomplete dominance and codominance; penetrance and expressivity;pleiotropy and heterogeneity;
polygenic and mulitfactorial.I.
II. THE EMERGING ROLE OF GENETICS AND GENOMEICS IN MEDICINE
Genetics, the study of inheritance, will play a critical role in future health care and medicine. The human genome project has triggered numerous genetic discoveries since its advent. New genetic information has allowed for the explanation of several physiological processes, both at the cellular & molecular level. In this chapter we will study the science of genetics and discuss inheritance patterns using specific diseases as examples. We will also discuss the new emerging science of genomics, which looks at the human body in terms of multiple, interacting genes.
A. GENETICS BACKGROUND
1. WHAT IS GENETICS?
Genetics is the study of INHERITANCE AND VARIABILITY.The term "genetics" is derived from the word "GENE".
2. WHAT IS A GENE? (Review from Chapter 4)
a. A gene codes for a particular heritable trait (or protein). o i.e. blood type, hair color, eye color etc.
b. Genes are carried on CHROMOSOMES that are composed of DNA (Deoxyribonucleic acid). See Fig 24.1, page 921.
c. A GENE (composed of DNA) is the portion of a chromosome that codes for a particular heritable trait (or protein).
d. More specifically, GENES TELL OUR CELLS WHICH PROTEINS TO MAKE.o PROTEINS HAVE MANY IMPORTANT
FUNCTIONS!!!!1. structure (Example = _____________________)2. transport (Example = _____________________)3. movement (Example = _____________________)4. chemical messengers (Example =
_____________________)5. defense (Example = _____________________)6. ENZYMES.
e. DNA HOLDS THE CODE FOR EVERY PROTEIN THAT MAKES US AND ALLOWS US TO FUNCTION!
I. THE EMERGING ROLE OF GENETICS AND GENOMEICS IN MEDICINE
A. GENETICS BACKGROUND
2. WHAT IS A GENE?
f. If there is an error in the DNA code (i.e. in a gene), this is called a MUTATION.
o If a mutation occurs in a gene, the end-product, the protein will be altered or absent:
1. may not be made at all. See Fig 4.26, page 126.
E1E2 E3 E4
A B C D E
When an enzyme is lacking from a metabolic pathway, childhood storage diseases result.
In Tay-Sachs, PKU, Niemin-Pick's.
2. may have altered function. See Fig 24.2, page 922.In cystic fibrosis & sickle-cell anemia
3. may be produced in excess.In epilepsy, where excess GABA leads to excess norepinephrine.
3. HOW DO WE TRANSFER OUR GENES TO OUR OFFSPRING?(Review from chapter 22)a. The genetic information of living organisms is DNA
(deoxyribonucleic acid) that is carried on the genes of chromosomes.
b. In humans, each somatic (body) cell is diploid, which means the cell contains 46 chromosomes or 23 pairs.
c. Human sex cells or gametes, however, are haploid, which means the cell contains only 23 chromosomes.
d. Meiosis is the type of cell division that results in gametes that possess half the chromosome number of the parent cell (i.e. meiosis reduces the chromosome number by one-half). o Male sperm (haploid) = 23 chromosomes (1
set)o Female egg (haploid) = 23 chromosomes (1
set)o Fertilization
(zygote; diploid) = 46 chromosome (2 sets).
I. THE EMERGING ROLE OF GENETICS AND GENOMEICS IN MEDICINE
A. GENETICS BACKGROUND
4. Development following Fertilization
a. The zygote formed by fertilization will divide into 2, 4, 8, 16, 32, 64 ... billions of cells to make up a human organism, however the DNA/genes/chromosomes will be identical in every one of those billion cells.
b. If a mutation exists in the zygote, it will also be in every one of those billion cells in the human organism.
c. If a problem occurs during meiosis, a sperm or egg may have too many or too few chromosomes, and result in a zygote with more or less than 46 chromosomes:
o 24 egg + 23 sperm = 47 chromosome zygote
1. Down's (trisomy 21), 2. Patau's (trisomy 13), 3. Edward's (trisomy 18 ).
o 23 egg + 22 sperm = 45 chromosome zygote1. Turner Syndrome.
II. THE HUMAN KARYOTYPE: See Fig 24.4, page 925.
A. Chromosomes and Genes Come in Pairs
1. As humans, most of our body cells contain 46 chromosomes:a. 23 (1 set) from mom;b. 23 (1 set) from dad.
2. A map of these chromosomes is called a karyotype.a. Our chromosomes are paired.
o homologous chromosomes.b. We possess 22 homologous pairs of autosomes:
o These chromosomes carry the genes for most of our traits (proteins).
c. We possess 1 pair of sex chromosomes:o Females have a homologous XX pair.o Males have a non-homologous XY pair.
See Fig 24.12, page 931.
II. THE HUMAN KARYOTYPE: See Fig 24.4, page 925.
A. Chromosomes and Genes Come in Pairs
3. The karyotype of a fetus can be obtained by a pre-natal test called an amniocentesis where any chromosomal abnormalities can be detected.
4. A gene codes for a heritable trait (or protein).a. hair colorb. eye colorc. blood type
5. Alleles are alternate forms of genes.a. The gene for eye color has several alleles. Two major alleles are:
o browno blue
b. Some alleles are dominant over others:o Brown is dominant over blue.
1. The dominant allele brown is written as an upper case letter (B);
2. The recessive allele blue is written as a lower case letter (b).
c. We inherit one (1) allele of a gene from each parent and therefore have two (2) alleles for each gene.
o If we inherit identical alleles, we are said to be homozygous for the trait.1. BB = homozygous dominant;2. bb = homozygous recessive.
o If we inherit two different alleles, we are said to be heterozygous for the trait.1. Bb = heterozygous.
6. PHENOTYPE VS. GENOTYPE
a. The phenotype is the expressed trait.o brown eyeso blue eyes
b. The genotype is the genetic makeup of the trait:o BB or homozygous dominanto Bb or heterozygous
II. THE HUMAN KARYOTYPE: See Fig 24.4, page 925.
B. Dominant and Recessive Inheritance
1. If brown eyes are dominant over blue eyes, predict the offspring of a cross between two individuals who are heterozygous for eye color.
a. Interpret given information: What are the genotypes and resulting cross of these two individuals?
o Brown = B; Blue = b.
o Individual 1 =_______(Bb); Individual 2 = _____(Bb).
o Therefore cross would be _______ x _______.(Bb x Bb)
b. What allele(s) would be present in each of the individuals' sex cells? o Individual 1 = ½ ____(B) & ½ _____(b);
o Individual 2 = ½ ____(B) & ½ _____(b).
c. Set up a Punnett Square illustrating the possible crosses
B b
B BB Bb
b Bb bb
d. Interpret the results of the cross:
o The genotypic ratio would be: 1. one (1) homozygous dominant (BB) individual : 2. two (2) heterozygous (Bb) individuals : 3. one (1) homozygous recessive (bb) individual.
o The phenotypic ratio would be:1. three (3) individual with brown eyes:2. one (1) individual with blue eyes.
II. THE HUMAN KARYOTYPE: See Fig 24.4, page 925.
B. Dominant and Recessive Inheritance
2. In humans, widow's peak is dominant over straight hairline. Predict the offspring of the cross between an individual who is homozygous dominant for hairline, with an individual who is homozygous recessive for hairline.
a. Interpret given information:
o Widow’s peak = W; Straight hairline = w.
o Therefore the cross is: _________ x ___________. (WW) (ww)
b. Determine alleles in sex cells:
o All of WW’s alleles would be _______(W);o All of ww’s alleles would be _______ (w).
c. Set up a Punnett Square:
W W
w Ww Ww
w Ww Ww
d. Interpret results:o Genotypic Ratio: All individuals are heterozygous for
hairline.o Phenotypic Ratio: All individuals have widow’s peaks.
II. THE HUMAN KARYOTYPE
C. MODES OF INHERITANCE:
1. Whether a trait is dominant or recessive, autosomal or sex-linked is called its mode of inheritance.
2. The mode of inheritance has important consequences in predicting the chance that offspring will inherit an illness or trait.
3. Three important rules:a. Autosomal Conditions are equally likely to affect both sexes.
o Sex-linked characteristics affect males much more often than females.
b. Recessive conditions are usually inherited from two healthy heterozygous parents (carriers). o Recessive conditions "skip" generations.
c. Dominant conditions are inherited by at least one affected parent.o Dominant conditions do not skip generations.
4. Example Using Cystic Fibrosis: See Fig 24.5, page 926.
a. Autosomal Recessive Inheritance;o Both parents are heterozygous (carriers); i.e. they have one
normal & one mutant allele; genotype = + , cf o What alleles would be present in the female’s eggs?
1/2 = ________(+) , 1/2 = _________(cf)
o What alleles would be present in the male’s sperm?
1/2 = ________(+) , 1/2 = _________(cf)
o What are the chances that parents who are heterozygous for cf will have an afflicted child?
+ cf
+ + + + cf
cf + cf cf cf
o Results: These parents have1. _____ (1/4) chance of having a normal child (+,+) ; 2. ______ (½) chance of having a child who is carrier
of CF (+, cf) ; 3. _______ (1/4) chance of having a child with CF (cf,
cf).
II. THE HUMAN KARYOTYPE
C. MODES OF INHERITANCE:
5. Example Using Huntington Disease: See Fig 24.6, page 927.
a. Autosomal Dominant Inheritance;
o Parents' genotypes?
1. Affected parent = + , HD2. Unaffected parent = + , +
o Alleles or Sex cells?
1. Affected parent: ½_____ (+), ½ _____ (HD);2. Unaffected parent: ½ _____ (+), ½ _____ (+).
o What are the chances that a male who carries the Huntington's gene & a normal female will have an afflicted child?
+ HD
+ + + + HD
+ + + + HD
o Results: These parents have the chance of having
1. ___________ (½) their offspring that carry the allele for Huntington disease and therefore those children will develop the disease during mid-life and
2. ____________(½) their offspring who do not carry the HD allele and therefore will be normal.
II. THE HUMAN KARYOTYPE
C. MODES OF INHERITANCE:
6. Example Using Sickle Cell Anemia (or disease) in which one of the four amino acid chains in hemoglobin is incorrect causing sickling of erythrocytes.
a. Incomplete Dominant Inheritance.
o The heterozygous (carrier) parents express a moderate form of the disease; called sickle cell trait.
o What are the chances that a male with sickle cell trait & a normal female will have an afflicted child, either with sickle cell anemia or sickle cell trait.
o Male: HbA, HbS
o Female: HbA. HbA
o Sperm: 1/2 = ______( HbA), 1/2 = ______( HbS)
Eggs: 1/2 = ______( HbA), 1/2 = ______( HbA)
o Punnett Square:
HbA HbS
HbA HbA HbA HbA HbS
HbA HbA HbA HbA HbS
o Results: These parents have the chance of having
1. _______ (½) their offspring that carry sickle cell trait,
2. ________(½) their offspring of being normal.
See Fig 24.7, page 928, which illustrates incomplete inheritance involved in plasma cholesterol levels.
II. THE HUMAN KARYOTYPE
C. MODES OF INHERITANCE:
7. Different Dominance Relationships
a. Incomplete dominanceo Results if heterozygote exhibits a phenotype halfway
between dominant and recessiveo Person has about half of a particular protein that a
homozygous dominant person would have
b. Codominanto Results when both alleles are expressedo Example is AB blood type
III. GENE EXPRESSION - how a gene affects phenotype
A. Penetrance and Expressivity
1. Penetrance – phenotype presentation
a. Whether or not the allele is seen in phenotypeb. Completely penetrant = all who have allele have traitc. Incompletely penetrant = only some with allele show trait
o Numerically, 50% penetrance = 50 out of 100 who have allele have trait
2. Expressivity – how much the phenotype is expressed
a. Sometimes variable intensity is seen in different peopleb. For example some people with polydactyly have 1 extra digit,
some have 4 extra digits
B. Pleiotropy
1. When a single genotype affects many phenotypes2. due to protein having many locations and functions
C. Genetic Heterogeneity
1. When more that one genotype causes the same phenotype2. For example, many different clotting disorders (genotype) are known, but
they all have the same symptoms (phenotype)
IV. COMPLEX TRAITS
A. Polygenic Traits1. Determined by more than one gene.2. Height, skin color, eye color are polygenic3. See Fig 24.8, page 929 and 24.9 page 930.
B. Multifactorial Traits1. Determined by more than one gene (polygenic) and environment.2. Height is Multifactorial because it is polygenic plus nutrition plays a role3. See Fig 24.8, page 929 and 24.9 page 930.
V. MATTERS OF SEX
A. Sex Determination: See Fig 24.11, page 931.
1. In sexually reproducing animals, two types of chromosomes exist:
a. Most pairs are called autosomes which determine most traits;b. One pair represents the sex chromosomes, which determine sex of
the individual. o Female = XX;o Male = XY. See Fig 24.14, page 935.
2. Following gametogenesis (sex cell formation; meiosis):
a. In females, the ova (gametes) contain 22 autosomes and the X sex chromosome. All ova contain the X chromosome.
XXX (ova)
b. In males, the sperm contain 22 autosomes, but o half the sperm carry the X sex chromosome and o the other half of the sperm contain the Y sex chromosome:
XYX or Y (sperm)
c. During fertilization, the chance of:o an X sperm and the X ova fusing to produce a female (XX)
is 50%;o a Y sperm and the X ova fusing to produce a male (XY) is
50%.
V. MATTERS OF SEX
B. Sex Chromosomes and Their Genes
Example Using Hemophilia in which a clotting factor is missing that leads to bleeding disorders.
1. Sex-linked Inheritance
a. Traits transmitted on the X chromosome are said to be sex-linked (or X-linked).
b. Males need only one copy of a mutant allele to possess the disorder; XaY.
c. Females need two copies of the mutant allele to be affected (XaXa); however if they have one mutant allele, they are carriers of the disease (XaX0).
d. What are the chances that a female hemophilia carrier and normal male will have a child afflicted with the disease?
o Genotypes of parents:1. Female = XHXh;2. Male = XhY.
o Alleles of parents:1. Female’s are ½ XH and ½ Xh;2. Males are ½ Xh; and ½ Y.
o Punnett square:
XH Xh
Xh XH Xh Xh Xh
Y XHY Xh Y
o Results: These parents have the chance of having
1. ______ (½) their female offspring as hemophilia carriers and
2. _______ (½) their female offspring as normal, and the chance of having
3. _______ (½) of their male offspring afflicted with hemophilia and
4. _______ (½) their male offspring as normal.
V. MATTERS OF SEX
C. Gender Effects on Phenotype
1. Sex-limited Traits
a. Only tend to affect certain sexb. Reason that a woman doesn’t grow a thick beard, but her son’s can
2. Sex-influenced Traits
a. Traits that are dominant in one sex but recessive in the otherb. Due to hormonal differencesc. Reason that more men are bald than women
VI. CHROMOSOMAL DISORDERS
A. Polyploidy = more than two sets of chromosomes.
1. Triploid = three sets of chromosomes or 69 (rather than 46); a. results in death as embryo or fetus.
B. Aneuploidy = missing one or having one extra chromosome. See Figure 24.14, page 935.
1. Trisomy 21 = Down Syndrome: See Clinical Application 24.2 on pages 936.
a. most common autosomal aneuploid event;
b. Characteristics:o short statureo straight sparse hairo protruding tongue; thick lipso reflexes/muscle tone pooro development slow o warm, loving personalitieso enjoy art & music
c. Intelligence varies greatlyo profound mental retardation too following simple directions too reading & using a computer
d. Many physical problems:o 50% die before 1st birthday
1. kidney defects2. heart defects3. digestive blockage
o Child with Down's is 15 times more likely to develop leukemia.
o Those who live past 40, develop amyloid protein in their brains (similar to Alzheimer's).
Likelihood of giving birth to a child with Down's increases drastically with maternal age. See Table 24A, page 936.
VII. GENETIC TESTING and GENETIC COUNSELING
A. PRENATAL GENETIC TESTINGSee Fig 24.15, page 938 and Table 24.2, page 937.
1. AMNIOCENTESISa. indicated in women:
o over the age of 35,o who have already given birth to a child with a
chromosomal abnormality, o whose family history (paternal included) shows any sign of
genetic disease.
b. performed after 14th week gestation;o Needle is inserted into amnionic sac and 5ml of fluid
containing fetal cells is extracted.
c. Cells are analyzed by karyotyping.o Useful in detecting many genetic disorders.o 0.5% chance of miscarriage
2. CHORIONIC VILLUS SAMPLING
a. performed as early as 8 weeks gestationb. 1-2% spontaneous abortion rate
3. FETAL CELL SORTING
a. involves obtaining and analyzing rare fetal cells in maternal circulation.o These cells may be responsible for autoimmune disorders
including scleroderma (see Chapter 16).
B. GENETIC COUNSELING
1. Because of the unique ethical questions and dilemmas that can result from genetic testing, genetic counseling is highly recommended for couples during this time. A genetic counselor:
2. obtains a complete family history.3. determines recurrence risks for certain conditions in specific relatives.4. provides information on the illness so families can make informed medical
decisions.5. discusses available tests and costs.6. discusses options.
VIII. GENE THERAPY
Gene therapy corrects the genetic defect causing disease symptoms.Two types:
A. Heritable Gene Therapy
1. alters all genes of individual2. must be performed on a fertilized egg or zygote3. not being performed in humans, but has shown some success in animal
models.
B. Nonheritable Gene Therapy
1. targets affected cells (not all cells) of an afflicted individual
a. Bone marrow transplants may be used to add an absent enzyme to particular blood cells (ADA deficiency);
b. Aerosols may be used to treat cystic fibrosis patients by introducing a functional CFTR gene.
c. Injection of certain proteins directly into tumors.
See Figure 24.17, page 942, which shows the many body locations where gene therapy is being used and for which diseases gene therapy has shown promise.
C. Requirements for Approval of Clinical Trial for Gene Therapy
1. Knowledge of defect and how it causes symptoms2. Animal model3. Success in human cells growing in vitro;4. Either the lack of alternate therapies or where existing therapies have not
been successful;5. Experiments must be safe.
D. Gene Therapy Concerns
1. Which cells should be treated?2. What proportion of the targeted cell population must be corrected to
alleviate or halt progression of symptoms?3. Is overexpression of the therapeutic gene dangerous?4. If the engineered gene “escapes” and infiltrates other tissues, is there
danger?5. How long will the affected cells function?6. Will the immune system attack the introduced cells? See Clinical Application 24.3, pages 940 and 941, which discuss some successes and setbacks with gene therapy.
IX. GENOMICS AND A NEW VIEW OF ANATOMY AND PHYSIOLOGY
A. The human genome consists of at least 40,000 protein-encoding genes.
1. The human genome project has triggered numerous genetic discoveries since its advent.
2. Knowing the human genome sequence has made it possible to view physiology at the microscopic level, as a complex interplay between gene functions.
B. The science of genomics looks at the human body in terms of multiple, interacting genes, rather than the field of genetics which deals mostly with single genes.
Fig 24.3, page 923 views genomics at the whole body, cellular, and microscopic level.
X. OTHERS:
A. Introduction on page 920, which provides a look into the future of genetics and how DNA “chips” may be used to prevent and/or treat genetic disease.
B. Clinical Application 24.1: “It’s all in the Genes”, page 924, which discusses several common human traits that are determined by a single gene.
C. Figure 24.8, page 929, which illustrates the continuously varying nature of height.
D. Figure 24.9, page 930, which illustrates variations in skin color using a model of three genes.
E. Figure 24.10, page 930, which illustrates variations in eye color using a model of two genes with two alleles each.
F. Figure 24.13, page 933, which illustrates pattern baldness as a “sex-influenced” trait.
Chapter 24: Genetics and Genomics
I. The Emerging Role of Genetics and Genomics in MedicineA. Genetics is the study of inheritance of characteristics.
B. Genes are sequences of nucleotides of the nucleic acid DNA.
C. Chromosomes are rod shaped structures that carry genes.
D. A gene’s nucleotide sequence tells a cell how to link a certain sequence of amino acids together to
construct a specific protein molecule.
E. A genome is the complete set of genetic instructions in a human cell.
F. Somatic cells have two sets of chromosomes.
G. Diploid means having two sets of chromosomes or 46 chromosomes.
H. Sex cells have one set of chromosomes.
I. Haploid means having one set of chromosomes or 23 chromosomes.
J. Genomics is the study of the human body in terms of multiple, interacting genes.
K. Proteonomics focuses on the spectrum of proteins that specific cell types produce.
L. Environmental factors that affect how genes are expressed are chemical, physical, social, and biological.
II. Modes of InheritanceA. Introduction
1. The probability that a certain trait will occur in the offspring of two individuals can be determined by knowing how genes are distributed in meiosis and the combinations in which they can come together at fertilization.B. Chromosomes and Genes Come in Pairs
1. Karyotypes are chromosome charts that display the 23 chromosome pairs in size order.
2. Autosomes are chromosome pairs 1 through 22 and do not carry genes that determine sex.
3. Sex chromosomes are chromosome pair 23 and determine sex.
4. Most chromosomes contain hundreds of thousands of genes.
5. Alleles are variant forms of genes.
6. Homozygous alleles are identical.
7. Heterozygous alleles are different.
8. Genotype is the particular combination of genes in a person’s genome.
9. Phenotype is the appearance or health condition of the individual that develops as a result of
the ways the genes are expressed.
10. A wild type allele is associated with the most common or normal phenotype.
11. A mutant allele is a change from the wild type.
C. Dominant and Recessive Inheritance
1. A dominant allele is one that masks that of another allele.
2. A recessive allele is one that is masked by a dominant allele.
3. An autosomal gene is located on a nonsex chromosome.
4. An X-linked gene is located on an X chromosome.
5. A Y-linked gene is located on a Y chromosome.
6. Mode of inheritance refers to whether a trait is dominant or recessive, autosomal or carried on a
sex chromosome.
7. An autosomal condition is equally likely to affect either sex.
8. X-linked characteristics affect males much more than females.
9. Recessive conditions can skip a generation because a person most likely inherits a recessive
condition from two healthy parents who are each heterozygotes.
10. Dominant conditions do not skip generations because a person who inherits the condition has
at least one affected parent.
11. The disease cystic fibrosis is an example of an autosomal recessive disorder.
12. If both parents are heterozygotes for the trait that causes cystic fibrosis, there is a 25% chance
that their offspring will be homozygous dominant, a 50% chance their offspring will be
heterozygous, and a 25% chance their offspring will be homozygous recessive.
13. A Punnet square is a table used to predict the probabilities of particular genotypes occurring
in offspring.
14. A pedigree is a diagram that depicts family relationships and genotypes and phenotypes when
they are known.
15. An example of an autosomal dominant disorder is Huntington disease.
D. Different Dominance Relationships
1. Incomplete dominance is a type of inheritance in which the heterozygous phenotype is
intermediate between that of either homozygote.
2. An example of a trait inherited through incomplete dominance is familial
hypercholesterolemia.
3. Codominant means different alleles are both expressed in a heterozygotes.
4. The genotypes of individuals with the following blood types are:
type A – IAIA or IAi
type B – IBIB or IBi
type AB - IAIB
type O - ii
III. Gene ExpressionA. Introduction
1. The same allele combination can produce different phenotypes because of the influences of
nutrition, toxins, illnesses or the activities of other genes.
2. A major goal of genomics is to identify and understand the interactions of alleles, nutrition,
environmental factors, illnesses, and activities of other genes.
B. Penetrance and Expressivity
1. Completely penetrant means that everyone who inherits it has some symptoms.
2. Incompletely penetrant means some individuals do not express the phenotype.3. A phenotype is variably expressive if the symptoms vary in intensity in different people.C. Pleiotropy
1. Pleiotropy is a single genetic disorder that can produce several symptoms.
2. An example of a disease that exhibits pleiotropy is Marfan syndrome.
D. Genetic Heterogeneity
1. Genetic heterogeneity is when the same phenotype may result from the actions of different
genes.
2. An example of a condition that exhibits genetic heterogeneity is hereditary deafness.
IV. Complex TraitsA. Monogenic means the traits are determined by a single gene and their expression is not greatly
influenced by the environment.
B. Polygenic means the traits are determined by more than one gene.
C. Variations in height are due to multiple genes.
D. Variations in skin color are due to three or more genes with two alleles each.
E. Variations in eye color are due to two genes, with two alleles each.
F. Complex traits are traits molded by one or more genes plus the environment.
G. Examples of complex traits are height, skin color, and certain illnesses.
V. Matters of SexA. Introduction
1. A human female is termed homogametic because she has two of the same type of sex chromosome.2. A human male is termed heterogametic because his two sex chromosomes are different.B. Sex Determination
1. A male is conceived when a sperm containing a Y chromosome fertilizes and egg (which has
an X chromosome).
2. A female is conceived when a sperm containing an X chromosome fertilizes and egg.
3. The gene responsible for being male is the SRY gene.
C. Sex Chromosomes and Their Genes
1. The X chromosome has more than 1000 genes.
2. The Y chromosome has only a few dozen genes.
3. The three groups of Y-linked genes are genes at the tips of the Y chromosome that have
counterparts on the X chromosome, genes that are very similar in DNA sequence to certain genes
on the X chromosome, and genes that are unique to the Y chromosome.
4. Y-linked genes are transmitted from father to sons.
5. Any gene on the X chromosome of a male is expressed in his phenotype because he has no
second allele on a second X chromosome to mask its expression.
6. An allele on an X chromosome of a female may or may not be expressed because it depends on
whether it is dominant or recessive and upon the nature of the allele on the second X chromosome.
7. The male is said to be hemizygous for X-linked traits because he has half the number of genes
on the X chromosome that the female has.
8. Examples of X-linked recessive traits are red-green color blindness and hemophilia.
9. If a mother is heterozygous for a particular X-linked gene, her son has a 50% chance of
inheriting either allele from her.
10. X-linked genes are passed on from mother to son.
11. A daughter can inherit an X-linked disorder only if her father is affected and her mother is a
carrier.
D. Gender Effects and Phenotypes
1. A sex-linked trait is one that affects a structure or function of the body that is present in only
males or only females.
2. Sex-influenced inheritance is a type of inheritance in which an allele is dominant in one sex but
recessive in another.
3. A heterozygous male is bald and a heterozygous female is not bald because the baldness allele
is dominant in males but recessive in females.
4. Genomic imprinting is an effect in which the expression of a disorder differs depending upon
which parent transmits the disease-causing gene.
VII. Chromosome DisordersA. Polyploidy
1. Polyploidy is the condition of having an extra set of chromosomes.
2. Polyploidy results from formation of a diploid gamete.
3. The fate of a polyploid human is death as an embryo or fetus.
B. Aneuploidy
1. Aneuploid means a condition of missing a chromosome or having an extra one.
2. Euploid means a normal chromosome number.
3. Anueploidy results from nondisjunction.
4. Nondisjunction is meiotic error in which a chromosomal pair fails to separate, producing a
sperm or egg that has two copies of a particular chromosome or none.
5. Autosomal aneuploidy often results in mental retardation.
5. Trisomy is the condition of having one extra chromosome.
6. Monosomy is the condition of missing one chromosome.
7. Translocation is a type of aberration in which one copy of a chromosome exchanges parts with
a different chromosome.
8. Trisomy 21 is known as Down syndrome.
9. Other common autosomal trisomies are trisomy 13 and trisomy 18.
10. Turner syndrome results from missing one X chromosome.
11. Klinefelter syndrome results from having an extra X chromosome.
12. Jacobs syndrome results from having an extra Y chromosome.
C. Prenatal Tests
1. An ultrasound can detect growth rate, head size, and size and location of organs.2. Amniocentesis is a procedure in which a needle is inserted into the amniotic sac to draw
amniotic fluid and can detect chromosomal abnormalities.
3. Chorionic villus sampling is of chorionic villus cells and can detect chromosomal
abnormalities.
4. Maternal serum markers can detect an underdeveloped fetal liver that may indicate an increased
risk of trisomy.
5. Fetal cell sorting is a process that separates and can detect genetic abnormalities.
VIII. Gene Therapy
A. Introduction
1. Functions of gene therapy are to alter, replace, silence or augment a gene’s function to improve
or prevent symptoms.
2. Gene therapy operates at the gene level.
B. Two Approaches to Gene Therapy
1. Two basic types of gene therapy are heritable gene therapy and nonheritable gene therapy.
2. Heritable gene therapy is the type that introduces the genetic change into a sperm, egg or
fertilized egg, which corrects each cell of the resulting individual.
3. Heritable gene therapy is most commonly performed in plants.
4. Nonheritable gene therapy is the type that targets only affected cells and therefore cannot be
transmitted to the next generation.
5. A nonheritalbe gene therapy for cystic fibrosis is an aerosol containing a virus that has had its
pathogenic genes removed and a functional human CFTR gene added.
C. Tools and Targets of Gene Therapy
1. Introduction
a. Some tools of gene therapy are viruses, liposomes, and naked preparations of DNA.
b. The challenge in nonheritable gene therapy is to target sufficient numbers of affected
cells for a long enough time to exert a noticeable effect.
2. Bone Marrow
a. Bone marrow tissue includes the precursors of all mature blood cells types.
b. Many new gene therapy targets might be reached by bone marrow because stem cells
in bone marrow can also travel to other sites, such as muscle, liver, and the brain.
3. Skin
a. In the laboratory, skin cells grow well.
b. Skin grafts can be used to secrete therapeutic proteins into a person’s system.
4. Muscle
a. The reasons muscle tissue is a good target for gene therapy are because it comprises about half of the body’s
mass, is easily accessible, and is near a blood supply.
b. Treatments of Duchenne muscular dystrophy are delivery of functional genes to immature muscle cell or to
direct stem cell from bone marrow to muscle tissue where they differentiate and produce needed proteins.
5. Endothelium
a. Endothelium is a tissue that forms capillaries and lines the interiors of other blood
vessels.
b. Endothelium can be altered to secrete a substance directly into the bloodstream.
6. Liver
a. The liver is a very important focus of gene therapy because it controls many bodily
functions and it can regenerate.
b. Liver cells that are genetically altered can relieve cholesterol buildup.
7. Lungs
a. The respiratory tract is an excellent candidate for gene therapy because an aerosol can
directly reach its lining cells, making it unnecessary to remove cell, alter them, and
reimplant them.
b. A form of gene therapy used to treat emphysema is inhalation of alpha-1-antitrypsin.
8. Nerve Tissue
a. Gene therapy of neurons is not feasible because these cells do not divide.
b. Routes of nerve cell gene therapy could include altering neuroglial cells or sending in
a valuable gene attached to the herpes simplex virus, which remains in nerve cells after
infections.
9. Gene Therapy Against Cancer
a. Glioma is a brain tumor.
b. A gene therapy approach for glioma is to infect fibroblasts with a virus bearing a gene
from a herpes virus that makes the cell sensitive to a drug called ganciclovir. The altered
fibroblasts are implanted near the tumor.
c. Another genetic approach to battling cancer is to enable tumor cells to produce
immune system biochemicals or to mark them so that the immune system more easily
recognizes them.
D. CODA
1. Gene discoveries have shed light on how the body normally functions.
2. Gene products interact with each other and environmental factors in intricate ways to build the
bodies of humans and other multicellular organisms.
Chapter 24: Genetics and Genomics
I. The Emerging Role of Genetics and Genomics in MedicineA. Genetics is___________________________________________________________________________
B. Genes are____________________________________________________________________________
C. Chromosomes are______________________________________________________________________
D. A gene’s nucleotide sequence tells a cell____________________________________________________
_______________________________________________________________________________________
E. A genome is__________________________________________________________________________
F. Somatic cells have_____________________________________________________________________
G. Diploid means________________________________________________________________________
H. Sex cells have_________________________________________________________________________
I. Haploid means_________________________________________________________________________
J. Genomics is___________________________________________________________________________
K. Proteonomics focuses on________________________________________________________________
_______________________________________________________________________________________
L. Environmental factors that affect how genes are expressed are___________________________________
_______________________________________________________________________________________
II. Modes of InheritanceA. Introduction
1. The probability that a certain trait will occur in the offspring of two individualscan be determined by________________________________________________________________________________________________________________________________B. Chromosomes and Genes Come in Pairs
1. Karyotypes are_________________________________________________________________
________________________________________________________________________________
2. Autosomes are_________________________________________________________________
3. Sex chromosomes are____________________________________________________________
________________________________________________________________________________
4. Most chromosomes contain__________________________________________________genes.
5. Alleles are_____________________________________________________________________
6. Homozygous alleles are__________________________________________________________
7. Heterozygous alleles are__________________________________________________________
8. Genotype is____________________________________________________________________
9. Phenotype is___________________________________________________________________
10. A wild type allele is____________________________________________________________
11. A mutant allele is______________________________________________________________
C. Dominant and Recessive Inheritance
1. A dominant allele is_____________________________________________________________
2. A recessive allele is_____________________________________________________________
________________________________________________________________________________
3. An autosomal gene is located______________________________________________________
4. An X-linked gene is located_______________________________________________________
5. A Y-linked gene is located________________________________________________________
6. Mode of inheritance refers to______________________________________________________
________________________________________________________________________________
7. An autosomal condition is equally likely to affect______________________________________
8. X-linked characteristics affect_____________________________________________________
9. Recessive conditions can skip a generation because____________________________________
________________________________________________________________________________
10. Dominant conditions do not skip generations because_________________________________
________________________________________________________________________________
11. The disease___________________________________________is an example of an autosomal
recessive disorder.
12. If both parents are heterozygotes for the trait that causes cystic fibrosis, there
is a_______________________________chance that their offspring will be homozygous dominant,
a____________________________________________chance their offspring will be heterozygous,
and a_________________________________chance their offspring will be homozygous recessive.
13. A Punnet square is_____________________________________________________________
________________________________________________________________________________
14. A pedigree is__________________________________________________________________
________________________________________________________________________________
15. An example of an autosomal dominant disorder is____________________________________
________________________________________________________________________________
D. Different Dominance Relationships
1. Incomplete dominance is_________________________________________________________
________________________________________________________________________________
2. An example of a trait inherited through incomplete dominance is_________________________
________________________________________________________________________________
3. Codominant means______________________________________________________________
________________________________________________________________________________
4. The genotypes of individuals with the following blood types are:
type A
type B
type AB
type O
III. Gene ExpressionA. Introduction
1. The same allele combination can produce different phenotypes because____________________
________________________________________________________________________________
2. A major goal of genomics is______________________________________________________
________________________________________________________________________________
B. Penetrance and Expressivity
1. Completely penetrant means________________________________________________________________________________________________________________________2. Incompletely penetrant means_______________________________________________________________________________________________________________________3. A phenotype is variably expressive if_________________________________________________________________________________________________________________
C. Pleiotropy
1. Pleiotropy is___________________________________________________________________
________________________________________________________________________________
2. An example of a disease that exhibits pleiotropy is_____________________________________
D. Genetic Heterogeneity
1. Genetic heterogeneity is__________________________________________________________
________________________________________________________________________________
2. An example of a condition that exhibits genetic heterogeneity is__________________________
________________________________________________________________________________
IV. Complex TraitsA. Monogenic means_____________________________________________________________________
B. Polygenic means______________________________________________________________________
C. Variations in height are due to____________________________________________________________
_______________________________________________________________________________________
D. Variations in skin color are due to_________________________________________________________
_______________________________________________________________________________________
E. Variations in eye color are due to__________________________________________________________
_______________________________________________________________________________________
F. Complex traits are______________________________________________________________________
G. Examples of complex traits are___________________________________________________________
V. Matters of SexA. Introduction
1. A human female is termed homogametic because________________________________________________________________________________________________________2. A human male is termed heterogametic because_________________________________________________________________________________________________________B. Sex Determination
1. A male is conceived when________________________________________________________
________________________________________________________________________________
2. A female is conceived when_______________________________________________________
________________________________________________________________________________
3. The gene responsible for being male is______________________________________________
C. Sex Chromosomes and Their Genes
1. The X chromosome has_____________________________________________________genes.
2. The Y chromosome has_____________________________________________________genes.
3. The three groups of Y-linked genes are______________________________________________
________________________________________________________________________________
________________________________________________________________________________
4. Y-linked genes are transmitted from father to_________________________________________
5. Any gene on the X chromosome of a male is expressed in his phenotype because
________________________________________________________________________________
6. An allele on an X chromosome of a female may or may not be expressed because
________________________________________________________________________________
________________________________________________________________________________
7. The male is said to be hemizygous for X-linked traits because____________________________
________________________________________________________________________________
8. Examples of X-linked recessive traits are____________________________________________
________________________________________________________________________________
9. If a mother is heterozygous for a particular X-linked gene, her son has a____________________
______________________________________________chance of inheriting either allele from her.
10. X-linked genes are passed on from________________________________________________
11. A daughter can inherit an X-linked disorder only if____________________________________
________________________________________________________________________________
D. Gender Effects and Phenotypes
1. A sex-linked trait is_____________________________________________________________
________________________________________________________________________________
2. Sex-influenced inheritance is______________________________________________________
________________________________________________________________________________
3. A heterozygous male is bald and a heterozygous female is not bald because_________________
________________________________________________________________________________
4. Genomic imprinting is___________________________________________________________
________________________________________________________________________________
VII. Chromosome DisordersA. Polyploidy
1. Polyploidy is___________________________________________________________________
________________________________________________________________________________
2. Polyploidy results from__________________________________________________________
________________________________________________________________________________
3. The fate of a polyploid human is___________________________________________________
B. Aneuploidy
1. Aneuploid means_______________________________________________________________
2. Euploid means_________________________________________________________________
3. Anueploidy results from__________________________________________________________
4. Nondisjunction is_______________________________________________________________
________________________________________________________________________________
5. Autosomal aneuploidy often results in_______________________________________________
________________________________________________________________________________
5. Trisomy is_____________________________________________________________________
6. Monosomy is__________________________________________________________________
7. Translocation is________________________________________________________________
________________________________________________________________________________
8. Trisomy 21 is known as__________________________________________________________
9. Other common autosomal trisomies are______________________________________________
10. Turner syndrome results from____________________________________________________
11. Klinefelter syndrome results from_________________________________________________
12. Jacobs syndrome results from____________________________________________________
C. Prenatal Tests
1. An ultrasound can detect___________________________________________________________________________________________________________________________
2. Amniocentesis is_____________________________________________________________and
can detect________________________________________________________________________
3. Chorionic villus sampling is____________________________________________________and
can detect________________________________________________________________________
4. Maternal serum markers can detect_________________________________________________
________________________________________________________________________________
5. Fetal cell sorting is___________________________________________________________and
can detect________________________________________________________________________
VIII. Gene Therapy
A. Introduction
1. Functions of gene therapy are_____________________________________________________
________________________________________________________________________________
2. Gene therapy operates at_________________________________________________________
B. Two Approaches to Gene Therapy
1. Two basic types of gene therapy are________________________________________________
________________________________________________________________________________
2. Heritable gene therapy is_________________________________________________________
________________________________________________________________________________
3. Heritable gene therapy is most commonly performed in_________________________________
4. Nonheritable gene therapy is______________________________________________________
________________________________________________________________________________
5. A nonheritable gene therapy for cystic fibrosis is______________________________________
________________________________________________________________________________
C. Tools and Targets of Gene Therapy
1. Introduction
a. Some tools of gene therapy are________________________________________________________________
___________________________________________________________________________________________
b. The challenge in nonheritable gene therapy is__________________________________
_________________________________________________________________________
2. Bone Marrow
a. Bone marrow tissue includes_______________________________________________
b. Many new gene therapy targets might be reached by bone marrow because
_________________________________________________________________________
_________________________________________________________________________
3. Skin
a. In the laboratory, skin cells grow____________________________________________
b. Skin grafts can be used to_________________________________________________
_________________________________________________________________________
4. Muscle
a. The reasons muscle tissue is a good target for gene therapy are_______________________________________
___________________________________________________________________________________________
___________________________________________________________________________________________
b. Treatments of Duchenne muscular dystrophy are__________________________________________________
___________________________________________________________________________________________
5. Endothelium
a. Endothelium is__________________________________________________________
b. Endothelium can be altered to______________________________________________
_________________________________________________________________________
6. Liver
a. The liver is a very important focus of gene therapy because_______________________
_________________________________________________________________________
b. Liver cells that are genetically altered can relieve_______________________________
_________________________________________________________________________
7. Lungs
a. The respiratory tract is an excellent candidate for gene therapy because
___________________________________________________________________________________________
_________________________________________________________________________
b. A form of gene therapy used to treat emphysema is_____________________________
_________________________________________________________________________
8. Nerve Tissue
a. Gene therapy of neurons is not feasible because________________________________
_________________________________________________________________________
b. Routes of nerve cell gene therapy could include________________________________
_________________________________________________________________________
9. Gene Therapy Against Cancer
a. Glioma is______________________________________________________________
_________________________________________________________________________
b. A gene therapy approach for glioma is_______________________________________
_________________________________________________________________________
c. Another genetic approach to battling cancer is to_______________________________
_________________________________________________________________________
D. CODA
1. Gene discoveries have shed light on________________________________________________
________________________________________________________________________________
2. Gene products interact with_______________________________________________________
________________________________________________________________________________