genetic disorders and pedigrees - heartland...

BIOL 117 HYBRID

GENETIC DISORDERS03/24/2016

See BB for websites to access before doing this assignment!!!

Topics

I. Autosomal Single Gene Disorders.

A. Autosomal Recessive Traits.

B. Autosomal Dominant Traits.

-Worksheet

II. Sex-linked Disorders.

-Worksheet

III. Pedigrees.

-Worksheet

You must do these problems BY HAND. ALL WORK IS REQUIRED. When completed, bring the worksheets to the instructor’s office. Only turn in the worksheets.

Remember to put your name on ALL PAGES OF the worksheets.

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Terms

1. Autosome: Any chromosome other than the sex chromosomes (X & Y). Chromosome designated 1-22.

2. Sex chromosome: X or Y.

3. Allele: Alternate forms of the same gene.

4. Dominant: Trait will be expressed if one allele is present.

5. Recessive: Trait will be expressed only if two alleles are present (one from each parent).

6. Homozygous: Having two copies of the same allele for a particular gene.

7. Heterozygous: Having two different alleles for a particular gene.

8. Carrier: Person with only one copy of the disorder allele.

9. Genotype: Actual alleles a person inherited from the mother and father

10. Phenotype: Outward expression of the trait.

11. Punnett Square: A grid used to determine potential genotypes and phenotypes of offspring by combining the parents’ gametes.

Allele Symbols: Possible Genotypes:

Autosomal dominant: H (capital letter is dominant) HHHh

Autosomal recessive: h (lowercase) hh

Sex-linked: Xc XC XC

A gene on the X chromosome (X-linked) XC Xc

Xc Xc

XCYXcY

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I. Autosomal Single Gene Disorders

Thousands of autosomal, single gene disorders have been clinically characterized. They are caused by too much, too little, or abnormal proteins.

A. Autosomal Recessive

Examples of Disorders1. Adenosine Deaminase Deficiency (ADA): one form of SCID, “bubble boy” disease (chromosome 20).

a. Enzyme missing which is necessary for the immune system=s T cells to function.b. Results in lack of immunity = frequent, severe infections.c. First hereditary condition treated with gene therapy (1990).

2. Tay-Sachs Disease (chromosome 15)a. Progressive nervous system degeneration.b. A child is deaf and blind by one or two years- progressive mental retardation, loss of muscular control; usually die at age three or four.c. Caused by a mutation of the HEXA gene, which normally codes for the enzyme hexosaminidase A (necessary for proper nerve function).d. Rare in U.S. because predominant populations are screened for carriers; most carriers choose to avoid the birth of a child because there is no treatment.e. Common in French Canadians, certain Jewish populations, Pennsylvania Dutch, and Cajuns.

3. Cystic Fibrosis, CF (chromosome 7)a. The most common genetic disorder among Caucasians. About 1 in 25 Caucasians are estimated to be carriers. It is rare in African Americans and Asians. It affects about 30,000 children and adults in the U.S.

b. Deficiency of the protein cystic fibrosis transmembrane conductance regulator (CFTR). This protein is found in the membrane of cells. The normal function of this protein is to transport chlorine across the cell membrane. The dysfunctional gene results in abnormal salt transport across membranes.

c. Symptoms: salty sweat, increased mucus secretion in various ducts and tracts;pancreatic, liver, pulmonary, and digestive dysfunction; frequent severe infections; usually infertile; symptoms become more severe with age.

d. With present management (hitting the chest to clear infected secretions that accumulate in the lungs, taking replacement enzymes, and antibiotics to treat infections), average life expectancy is 40+ years.

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Determining the chances of passing on the allele and disorder.

Possible genotypes: Phenotype

CCNo cystic fibrosis

CcNo cystic fibrosis; but can pass on the allele to the offspring (carrier).

ccCystic fibrosis

Autosomal Recessive: Parents do not have to be affected to have an affected child; often skips generations.

Example Problem 1: One carrier parent and one homozygous recessive parent.

Cc x cc

Cc cc

PossibleGametes: C or c c

Use a punnett square to determine all possible offspring genotypes and phenotypes and their frequency probabilities.See next page for example punnett square.

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5

C

c

c

These are all possible sperm.

These are all possible eggs.

Cc

cc

These are all possible offspring genotypes.50% Cc, 50% cc

Example Problem 2: Two carrier parents.

Cc x cc

Cc Cc

PossibleGametes: C or c C or c

Use a punnett square to determine all possible offspring genotypes and phenotypes and their frequency probabilities.See below for example punnett square.

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C

c

c



CC

Cc

These are all possible offspring genotypes.

25% CC (no cystic fibrosis)

50% Cc (no cystic fibrosis, but a carrier)

25% (cystic fibrosis)

C

Cc

cc

B. Autosomal DominantExamples of Disorders

1. Huntington disease (chromosome 4)

a. Caused by an abnormal protein (huntingtin) whose exact normal function is unknown. b. Progressive nerve degeneration.c. Usually adult onset (35-45 years) of symptoms.d. Worsening gait, constant uncontrollable movements, personality changes...e. Death usually within 10-15 years after diagnosis.

2. Amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) (chromosome 21)

a. Affects 1 in 100,000 people worldwide, but only 10% of the cases are inherited. The other 90% are probably environmentally induced (don’t know cause).b. Fatal degenerative nerve disease.c. Stiffening and weakening of the legs and arms, become quadriplegic, die as respiratory muscles become paralyzed.d. Mutation in the gene for the enzyme superoxide dismutase, an anti-oxidant that detoxifies molecules (free-radicals) that damage tissue.

3. Achondroplasia: A form of dwarfism (chromosome 4)

4. Familial hypercholesterolemia (chromosome 19)

-This is one type of incomplete dominance.

-hh: Have normal amounts of molecules which remove cholesterol from the blood

-Hh: Have half the normal number of molecules that remove cholesterol from the blood; therefore, cholesterol builds up along the walls of

the arteries. Affected individuals can affect lifespan by monitoring diet

(Example: decreasing amount of cholesterol in diet can extend life).

-HH: Have very few molecules that remove cholesterol from the blood; usually die at a very young age of heart attack or stroke.

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Determining the chances of passing on the allele and disorder.

For autosomal dominant traits, only ONE copy of the mutated allele is required for an individual to be affected, and this can be inherited from either parent. Individuals with a dominant trait have a 1 in 2 chance of passing that allele, and, therefore, that trait, to each of their children. If a child is affected, one parent must be affected.

Example: Heterozygous mother and unaffected father

hh x Hh

hh Hh

PossibleGametes: h H or h

Use a punnett square to determine all possible offspring genotypes and phenotypes and their frequency probabilities.See below for punnett square.

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H

h



Hh hh

These are all possible offspring genotypes.50% Hh, 50% hh

h

Therefore, Predict that 50% of offspring would be affected by the dominant trait and 50% would not be affected.

Name: BIOL 117 Hybrid

Worksheet: Genetics Problems – Autosomal Traits

STEPS IN SOLVING GENETICS PROBLEMS:

1. Write down all of the known information:A. Dominant and recessive traits and symbolsB. Phenotypes and genotypes of parentsC. All possible gamete genotypesD. Set up a punnett squareE. Determine genotypes and phenotypes of offspring

2. Be sure to carefully determine and, IF NECESSARY, ANSWER IN WORDS, the exact question being asked.

Complete the following problems on this page. Follow ALL of the steps above.

YOU MUST SHOW ALL WORK. Points will be deducted for not showing work.

1. Freckles are an autosomal dominant trait. A woman with freckles (Ff) marries a man without freckles. What are the chances that their children will have freckles? (Answer in percentages).

2. Two freckled adults marry and have children. The first baby has no freckles. What are the genotypes of the parents?

3. In humans, normal pigmentation is due to a dominant gene A. Albinism is due to the recessive allele a. A man without albinism marries an albino woman and their first child is an albino. What are the genotypes of these 3 people?

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II. Sex-linked Disorders

Sex-linked disorders can be on either the X or Y chromosome. Since the X chromosome is larger and contains more genes, most sex-linked disorders are found on the X chromosome. Many are recessive. Y-linked genes also have been identified.

X-linked disorders Y-linked Disorders (Y only, no homologous gene on X)

One form of bipolar affective disorder is recessive X-linked (another form is autosomal recessive).

Several genes affect fertility and sex organ development. One gene called DAZ, if missing from the Y chromosome or mutated, will result in a low sperm count.

Hemophelia SRY gene (testes determining)Red-green color blindness Hairy ears?Duchene muscular dystrophySee Allele Symbols on page 2.

Example: Recessive X-linked trait. Carrier mother and Unaffected fatherXHXh x XHY

XHY XHXh

Possible XH or Y XH or Xh Gametes:

Punnett Square:

Name: BIOL 117 Hybrid10



XH

XH XH XH XH Xh

These are all possible offspring genotypes.

Xh

See punnett square below.

Predict that 0% of female and 50% of male offspring would be affected by the trait and would be affected.

Y XHY XhY

Worksheet: Genetics Problems – Sex-linked Traits

STEPS IN SOLVING GENETICS PROBLEMS:

1. Write down all of the known information:A. Dominant and recessive traits and symbolsB. Phenotypes and genotypes of parentsC. All possible gamete genotypesD. Set up a punnett squareE. Determine genotypes and phenotypes of offspring

2. Be sure to carefully determine and, IF NECESSARY, ANSWER IN WORDS, the exact question being asked.

Complete the following problems on the next page. Follow ALL of the steps above.

YOU MUST SHOW ALL WORK. Points will be deducted for not showing work.

1. In humans, red-green color-blindness is due to a recessive gene Xc. Normal vision results from the dominant gene XC. If a homozygous woman of normal vision marries a color-blind man, what type of vision will be expected in their children?

2. A X-linked gene in cats controls coat color. The XB allele produces black, and the Xb allele produces yellow. When heterozygous (XB Xb), the coat color is calico. If a yellow female cat has one yellow kitten and three calico kittens, 1) What is the sex of the yellow kitten? 2) What is the color of the father of these kittens? 3) What does this tell you about the sex of any calico cat?

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III. Pedigree: A diagram of a family history showing the occurrence of a trait

Pedigrees are helpful in determining whether a trait has a genetic component, and, if so, the pattern of inheritance (autosomal recessive, autosomal dominant, or sex-linked recessive).

Go through this animation: http://dnalc.org/view/15913-The-pedigree.html

Symbols are used in the diagram:

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Deceased female (affected by that trait and male (unaffected by the trait in question)

Affected femaleAffected male

Unaffected female

Vertical line: Parents leading to children

Horizontal lines connect parents or siblings

Unaffected male

http://dnalc.org/view/15913-The-pedigree.html

Clues to Pedigree Problems

A. When determining if a trait is sex-linked or autosomal…

1. An X-linked trait is usually expressed far greater in males since most are X-linked recessive. If X-linked, we will only consider X-linked recessive traits (none will be X-linked dominant).

2. Y-linked traits are only passed from father to son. Females are never affected. In this assignment, none of the traits are Y-linked.

3. An autosomal trait is expressed approximately equally in males and females.

B. When determining if an autosomal trait is dominant or recessive…

1. Dominant traits only require one allele to outwardly express the trait.

a. Dominant traits are often present in every generation.

b. If a child is affected, at least one parent must be affected.

2. Recessive traits require two alleles to outwardly express the trait.

a. Recessive traits often skip generations.

b. An affected child does not have to have an affected parent.

C. When attempting to determine the pattern of inheritance, scan the pedigree. Use the above clues to make an educated guess as to the most likely pattern of inheritance.

D. Use a PENCIL to write in the genotypes according to the pattern of inheritance you've chosen. If the genotype of the second allele is unknown, put a ? by the first allele.Continue writing in genotypes until an individual doesn't "fit". If one doesn't "fit", erase all of the genotypes, and try another pattern of inheritance using new genotypes.

Rule out each pattern of inheritance. It is a matter of exclusion.

Occasionally, with the limited information available, more than one pattern of inheritance may be included as ‘possible’.

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Queen Victoria of England was a carrier of the genefor hemophilia. She passed the harmful allele forthis X-linked trait on to one of her four sons and atleast two of her five daughters. Her son Leopold hadthe disease and died at age 30, while her daughterswere only carriers. As a result of marrying into otherEuropean royal families, the princesses Alice andBeatrice spread hemophilia to Russia, Germany, andSpain. By the early 20th century, ten of Victoria'sdescendents had hemophilia. All of them were men.

Queen Victoria(1819-1901)

It is assumed that a chance mutation in either the egg or sperm that came together to make Queen Victoria caused her to unknowingly be a carrier for the hemophilia allele (XX'). When she grew up, she married Prince Albert, who was normal XY. One would predict that ½ of their sons (¼ of their children) would be hemophiliacs and ½ of their daughters (¼ of their children) would be carriers. Their children married other royalty, and spread the gene throughout the royal families of Europe.

Carriers in the above pedigree have a half circle filled in.Try this animation out to test your understanding http://dnalc.org/view/16323-Problem-13-Mendelian-laws-apply-to-human-beings-.html

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ASSUME ALL SEX-LINKED ARE X-LINKED (NOT Y) AND ARE RECESSIVE.

Possible Patterns of Inheritance: 1. Autosomal Dominant, or 2. Autosomal Recessive, or 3. X-linked recessive

I. Determine the pattern of inheritance in the following pedigrees. Write correct genotypes for all of the individuals. If the genotype of the second allele is unknown, put a ? by the first allele.

Letter Symbols with respective traits: H= not affected h= affected

Correct pattern of inheritance: Autosomal Recessive OR (see next page!)

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EXAMPLE

hh

hh hh hh hh

Hh

H? H?

Hh Hh Hh Hh HhHh

H?

H?

1. Use the clues on page 13 to make an educated guess as to the pattern of inheritance. Here, autosomal recessive was our first ‘educated guess’ since it was not found in every generation (Parents did not have to be affected for offspring to be affected).

2. A letter was then chosen to represent dominant and recessive alleles. If the trait is autosomal recessive, affected individuals (with darkened symbols) would have to be hh. Since the dominant trait only requires one allele to be expressed, you may not know if the second allele is dominant or recessive. In that case, I put a ‘?’ by the dominant allele.

3. EVERY individual’s genotype (HH, Hh, hh or H?) is PENCILED in by each individual’s symbol. In this case, autosomal recessive ‘fit’ all of the individuals.

EXAMPLE

Remember to use the correct symbols when penciling in the genotypes over every person. Only sex-linked traits use X and Y symbols. Autosomal traits do not use X and Y, as the example on the previous page illustrates.

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XhY

XhY XhY XhY XhY

XHX?

XHXh

XHX?

XHXh

XHXh

XHYXHXhXHY XHY

XHY

XHY

X-LINKED RECESSIVE!

If you try sex-linked (X-linked recessive), you would find that this pattern of inheritance also fits. In this case, X-linked recessive may be the better choice since only males are affected.

Name: BIOL 117 Hybrid

Worksheet: PedigreesPedigree 1. Use H or h for the letter symbols of the alleles (or XH and Xh if sex-linked).

1. Using the clues, make an educated guess as to the correct pattern of inheritance (autosomal recessive, or autosomal dominant, or sex-linked recessive)

2. Pencil in genotypes for all individuals. Remember to use a ? if an allele is unknown.

3. If this pattern of inheritance ‘fits’, write the correct pattern at the bottom of the page. If it did not fit, erase the genotypes and try another pattern until you find one that does fit.

Write the correct pattern of inheritance (autosomal recessive, or autosomal dominant, or sex-linked recessive)

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Pedigree 2. Use H or h for the letter symbols of the alleles (or XH and Xh if sex-linked).





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Pedigree 3. Use H or h for the letter symbols of the alleles (or XH and Xh if sex-linked).





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