mendel and the gene idea

LECTURE PRESENTATIONSFor CAMPBELL BIOLOGY, NINTH EDITION

Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson

© 2011 Pearson Education, Inc.

Lectures byErin Barley

Kathleen Fitzpatrick

Mendel and the Gene Idea

Chapter 14

Genetic Principles

• What genetic principles account for the passing of traits from parents to offspring?

• the “blending” hypothesis genetic material from the two parents blends together – like blue and yellow paint blend to make green– over enough generations – you will get a uniform

population• the “particulate” hypothesis parents pass on discrete

heritable units (genes)– this hypothesis can explain the reappearance of traits

after “skipping” several generations

Mendel used the scientific approach to identify two laws of inheritance

• Mendel discovered the basic principles of heredity by breeding garden peas in carefully planned experiments

• region now part of the Czech Republic

• Olmutz Philosophical Institute• entered an Augustine

monastery in 1843 – 21 yrs old• one of his mentors – Christian

Doppler (proponent of the scientific method)

Mendel’s Experimental, Quantitative Approach

• Advantages of pea plants for genetic study– there are many varieties with distinct heritable features, or

characters - such as flower color• character variations (such as purple or white flowers) are

called traits– mating can be controlled through the control of pollination

• each flower has sperm-producing organs (stamens) and an egg-producing organ (carpel)

• could remove the reproductive parts of one plant before meiosis

– cross-pollination involved dusting one plant with pollen from another

• Mendel chose to track only those characters that occurred in two distinct alternative forms– e.g. either purple or white flowers

• he also started with varieties that were true-breeding – used plants that produced the same variety of offspring

over several generation of self-pollination– e.g. plant that makes white flowers - is true-breeding if

ALL the seed from that plant produce white flowers over several generations

– we know this is know called homozygous

Parentalgeneration(P)

Stamens

Carpel

First filialgenerationoffspring(F1)

TECHNIQUE

RESULTS

3

2

1

4

5

• in a typical experiment: Mendel mated two contrasting, true-breeding varieties– a process called hybridization

• called the true-breeding parents the P generation

• the hybrid offspring of the P generation were called the F1 generation

• when F1 individuals either self-pollinated or cross- pollinate with other F1 hybrids the F2 generation

The Law of Segregation

• when Mendel crossed true-breeding white- and purple-flowered pea plants all of the F1 hybrids were purple (100%)

• when Mendel crossed these F1 hybrids many of the F2 plants had purple flowers

• but some had white flowers• Mendel discovered a three to

one ratio of purple to white flowers in the F2 generation

P Generation

EXPERIMENT

(true-breedingparents)

F1 Generation(hybrids)

F2 Generation

Purpleflowers

Whiteflowers

All plants had purple flowers

Self- or cross-pollination

705 purple-flowered

plants

224 whiteflowered

plants

• Mendel reasoned that only the purple flower factor was affecting flower color in the F1 hybrids– called the purple flower color a

dominant trait – the white flower color a recessive trait

• the factor for white flowers was not diluted or destroyed because it reappeared in the F2 generation

• Mendel observed the same pattern of inheritance in six other pea plant characters - each represented by two traits

• what Mendel called a “heritable factor” is what we now call a gene

Mendel’s Model

• Mendel developed a hypothesis to explain the 3:1 inheritance pattern he observed in F2 offspring

• Four related concepts make up this model• these concepts can be related to what we now know

about genes and chromosomes

• alternate versions of genes account for variations in inherited characters– e.g. the gene for flower color in pea plants exists in two versions: one

for purple flowers and the other for white flowers• these alternative versions of a gene are now called alleles• each gene resides at a specific locus on a specific chromosome

– because we are diploid – the genetic locus is represented twice– one allele is found on each chromosome in the homologous pair– the same locus for each allele

Concept #1: Alleles

Allele for purple flowers

Locus for flower-color gene

Allele for white flowers

Pair ofhomologouschromosomes

• for each character - an organism inherits two alleles– one from each parent

• Mendel made this deduction without knowing about the role of chromosomes

• the two alleles at a particular locus may be identical– as in the true-breeding plants of Mendel’s P generation– now known as homozygous

• Or the two alleles at a locus may differ– as in the F1 hybrids – now known as heterozygous

Concept #2: Two Alleles are inherited

• if the two alleles at a locus differ- then one determines the organism’s appearance, and the other has no noticeable effect on appearance– the one that determines the appearance – dominant allele– the one that has no effect – recessive allele– we now call the appearance – the phenotype– the genotype – genetic makeup for that trait found in the

organism

• in the flower-color example- the F1 plants had purple flowers because the allele for that trait is dominant

Concept #3: Dominant vs. Recessive Alleles

• two alleles for a heritable character separate or segregate during gamete formation and end up in different gametes– an egg or a sperm gets only one of the two alleles that

are present in the organism• this segregation of alleles corresponds to the

distribution of homologous chromosomes to different gametes in meiosis

• in the law of independent assortment – this segregation is random

Concept #4: Law of Segregation

• Mendel derived the law of segregation by following a single character

• the F1 offspring produced Mendel’s first sets of experiments were monohybrids = individuals that are heterozygous for one character– heterozygous for two characters = dihybrids

• a cross between such heterozygotes is called a monohybrid cross

• Mendel’s segregation model accounts for the 3:1 ratio he observed in the F2 generation

• the possible combinations of sperm and egg can be shown using a Punnett square– a diagram for predicting the

results of a genetic cross between individuals of known genetic makeup

• a capital letter represents a dominant allele and a lowercase letter represents a recessive allele

P Generation

F1 Generation

F2 Generation

Appearance:Genetic makeup:

Gametes:

Appearance:Genetic makeup:Gametes:

Purple flowers White flowers

Purple flowers

Sperm from F1 (Pp) plant

Pp

PP pp

P

P

P

P

p

p

p

p

Eggs from F1 (Pp) plant

PP

ppPp

Pp

1/21/2

3 : 1

The Testcross

Dominant phenotype,unknown genotype:

PP or Pp?

Recessive phenotype,known genotype:

pp

Predictions

If purple-floweredparent is PP

If purple-floweredparent is Pp

or

Sperm Sperm

Eggs Eggs

or

All offspring purple 1/2 offspring purple and 1/2 offspring white

Pp Pp

Pp Pp

Pp Pp

pp pp

p p p p

P

P

P

p

TECHNIQUE

RESULTS

• How can we tell the genotype of an individual with the dominant phenotype?– such an individual could be either

homozygous dominant or heterozygous

• the answer is to carry out a testcross: breeding the mystery individual with a homozygous recessive individual– if any offspring display the

recessive phenotype - the mystery parent must be heterozygous

P Generation

F1 Generation

Predictions

Gametes

YYRR yyrr

yrYR

YyRr

Hypothesis ofdependent assortment

Hypothesis ofindependent assortment

Predictedoffspring ofF2 generation

Sperm

Spermor

EggsEggs

Phenotypic ratio 3:1

Phenotypic ratio 9:3:3:1

approximately 9:3:3:1315 108 101 32

1/21/2

1/2

1/2

1/41/4

1/41/4

1/4

1/4

1/4

1/4

9/163/16

3/161/16

YR

YR

YR

YRyr

yr

yr

yr

1/43/4

Yr

Yr

yR

yR

YYRR YyRr

YyRr yyrr

YYRR YYRr YyRR YyRr

YYRr YYrr YyRr Yyrr

YyRR YyRr yyRR yyRr

YyRr Yyrr yyRr yyrr

• Mendel identified his second law of inheritance by following two characters at the same time

• crossing two true-breeding parents differing in two characters produces dihybrids in the F1 generation

– heterozygous for both characters• a dihybrid cross = a cross between 2

F1 dihybrids– can determine whether two

characters are transmitted to offspring as a package or independently

– if two traits are linked – 3:1 F2 ratio– if two traits segregate independently

– 9:3:3:1 ratio

The Law of Independent Assortment

• using a dihybrid cross - Mendel developed the law of independent assortment– states that each pair of alleles segregates independently of

each other pair of alleles during gamete formation• strictly speaking- this law applies only to genes on

different, nonhomologous chromosomes or those far apart on the same chromosome

• genes located near each other on the same chromosome tend to be inherited together– tend to be linked

• genes far apart from each other tend to cross over– tend to be un-linked

The laws of probability govern Mendelian inheritance

• Mendel’s laws of segregation and independent assortment reflect the rules of probability

• when tossing a coin -the outcome of one toss has no impact on the outcome of the next toss

• in the same way, the alleles of one gene segregate into gametes independently of another gene’s alleles

Segregation ofalleles into eggs

Segregation ofalleles into sperm

Sperm

Eggs

1/2

1/2

1/21/2

1/41/4

1/41/4

Rr Rr

R

RR

RR

R

r

r

rr r

r

• the multiplication rule states that the probability that two or more independent events will occur together is the product of their individual probabilities– one event and another event will occur– e.g. chances of drawing a king (4/52 or 1/13) and it being a

heart (13/52 or 1/4) = 1/52• probability in an F1 monohybrid cross can be determined using

the multiplication rule • segregation in a heterozygous plant is like flipping a coin:

– each gamete has a 50% chance (1 out of 2 or ½) of carrying the dominant allele and a 50% chance of carrying the recessive allele

The Multiplication and Addition Rules Applied to Monohybrid Crosses

• the addition rule states that the probability that any one of two or more mutually exclusive events (i.e. “either or” events) will occur is calculated by adding together their individual probabilities– one event or another event will occur– e.g. draw a king or a seven from a deck of cards = 1/13 +

1/13 = 2/13

• the rule of addition can be used to figure out the probability that an F2 plant from a monohybrid cross will be heterozygous rather than homozygous

P Generation

F1 Generation

F2 Generation


Gametes:



Purple flowers


Pp

PP pp

P

P

P

P

p

p

p

p


PP

ppPp

Pp

1/21/2

3 : 1

• you can also use the multiplication rule on the F2 generations if you just want to look at genotype– Pp x Pp monohybrid cross – using a Punnett square – the

multiplication rule determines the genotypic frequency of each of the different offspring

– ½ of the gametes are P, ½ the gametes are p

– so the chances of getting the PP homozygote (i.e. the P gamete AND the P gamete) is ½ x ½ = ¼

P Generation

F1 Generation

F2 Generation


Gametes:



Purple flowers


Pp

PP pp

P

P

P

P

p

p

p

p


PP

ppPp

Pp

1/21/2

3 : 1

– if you want to know the chances of a heterozygote vs. a homozygote – use the addition rule

– chance of a homozygote • PP = ¼• OR pp = ¼• so ¼ + ¼ = ½

– chances of a heterozygote• Pp = ¼• OR pP = ¼• so ¼ + ¼ = ½

– So the addition rule gives you the total genotypic makeup AND the phenotypic probability within all offspring

– BUT using a Punnett square is easier

Solving Complex Genetics Problems with the Rules of Probability

• a dihybrid or other multi-character cross is equivalent to two or more independent monohybrid crosses occurring simultaneously

• in calculating the chances for various genotypes- each character is considered separately and then the individual probabilities are multiplied

• e.g. pea pod color and pea shape• e.g. probability of being yellow AND round –

multiplication rule – multiply the chances of being a yellow pea by the chances of being a round pea

• multiplication and additional rules are also used for dihybrid F1 crosses

• multiplication rule gives you the changes for each offspring

– e.g. YYRR = 1/16 – chances of being YY – ¼– chances of being RR – ¼– chances of being YY AND RR – ¼ x ¼

• what is the chance of a YyRR offspring showing up from a YyRr x YyRr F1 cross??

– gametes possibilities are all ¼ probabilities

– two YyRR offspring are found in the Punnett square – addition rule

• 1/16 + 1/16 = 2/16 or 1/8

P Generation

F1 Generation

Predictions

Gametes

YYRR yyrr

yrYR

YyRr




Sperm

Spermor

EggsEggs



approximately 9:3:3:1315 108 101 32

1/21/2

1/2

1/2

1/41/4

1/41/4

1/4

1/4

1/4

1/4

9/163/16

3/161/16

YR

YR

YR

YRyr

yr

yr

yr

1/43/4

Yr

Yr

yR

yR

YYRR YyRr

YyRr yyrr

YYRR YYRr YyRR YyRr

YYRr YYrr YyRr Yyrr

YyRR YyRr yyRR yyRr

YyRr Yyrr yyRr yyrr

• what are the chances of a yellow plant being made??– genotypes: YYxx OR Yyxx

• what are the chances of a yellow, round plant being made??

– genotypes: YYRR or YyRr or YyRR or YYRr

P Generation

F1 Generation

Predictions

Gametes

YYRR yyrr

yrYR

YyRr




Sperm

Spermor

EggsEggs



approximately 9:3:3:1315 108 101 32

1/21/2

1/2

1/2

1/41/4

1/41/4

1/4

1/4

1/4

1/4

9/163/16

3/161/16

YR

YR

YR

YRyr

yr

yr

yr

1/43/4

Yr

Yr

yR

yR

YYRR YyRr

YyRr yyrr

YYRR YYRr YyRR YyRr

YYRr YYrr YyRr Yyrr

YyRR YyRr yyRR yyRr

YyRr Yyrr yyRr yyrr

Chance of at least two recessive traits

ppyyRr

ppYyrr

Ppyyrr

PPyyrrppyyrr

1/4 (probability of pp) 1/2 (yy) 1/2 (Rr) 1/4 1/2 1/2 1/2 1/2 1/2 1/4 1/2 1/2 1/4 1/2 1/2

1/16

1/16 2/16

1/16

1/16

6/16 or 3/8

PpYyRr X Ppyyrr

In calculating the chances for various genotypes, each character is considered separately, and then the individual probabilities are multiplied

Inheritance patterns are often more complex than predicted by simple Mendelian genetics

• the relationship between genotype and phenotype is rarely as simple as in the pea plant characters Mendel studied

• many heritable characters are not determined by only one gene with two alleles

• However, the basic principles of segregation and independent assortment apply even to more complex patterns of inheritance

Extending Mendelian Genetics for a Single Gene

• inheritance of characters by a single gene may deviate from simple Mendelian patterns in the following situations:

– when alleles are not completely dominant or recessive– when a gene has more than two alleles– when a gene produces multiple phenotypes

Genes Affect Phenotype

• genes code for polypeptides• polypeptides become modified to form proteins• proteins function as enzymes, receptors, channels etc…• SO: when a gene is mutated – this can affect protein function

Dominant vs. Recessive Genotypes

• recessive mutations involve the loss of function– e.g. yellow vs. green peas; smooth vs. wrinkled

• have no major effect in the heterozygous form because the wild type allele specifies the normal polypeptide

• pea shape – gene called SBE (starch branching enzyme 1)– R active enzyme that catalyzes the conversion of

amylose to amylopectin (branched)– so with RR twice the amount of active enzyme;

twice the amount of amylopectin made– with Rr half the amount– with rr – no active enzyme; amylose remains

• less amylopectin builds up in the pea• more sucrose builds up• water enters the pea when young and exits when

mature wrinkled

Degrees of Dominance

• Complete dominance occurs when phenotypes of the heterozygote and dominant homozygote are identical

• Incomplete dominance = the phenotype of F1 hybrid is somewhere between the phenotypes of the two parental varieties

• Co-dominance = two dominant alleles affect the phenotype in separate, distinguishable ways

P Generation

F1 Generation

F2 Generation

1/21/2

1/21/2

1/2

1/2

Red White

Gametes

Pink

Gametes

Sperm

Eggs

CWCWCRCR

CR CW

CRCW

CR CW

CWCR

CR

CW

CRCR CRCW

CRCW CWCW

Incomplete Dominance

• snapdragons• red is dominant to white• when crossed they produce

heterozygotes that make pink flowers

• 1:2:1 ratio of phenotypes is the same as the 1:2:1 ratio of genotypes– because the heterozygote can be

distinguished from the parents• gene codes for an enzyme – amount

of the enzyme determines pigmentation of flower

– heterozygotes – make 50% of the enzyme so pigmentation is distinct

P Generation

F1 Generation

F2 Generation

1/21/2

1/21/2

1/2

1/2

Red White

Gametes

Pink

Gametes

Sperm

Eggs

CWCWCRCR

CR CW

CRCW

CR CW

CWCR

CR

CW

CRCR CRCW

CRCW CWCW

Co-Dominance

• occurs when the heterozygote shows characteristics found in each of the parental homozygotes

• produces a phenotype and genotype ratio of 1:2:1

• the phenotypes of both pure-breeding parental lines show up simultaneously in the F1 hybrid

• e.g. coloration in lentils

• a dominant allele does not subdue a recessive allele - alleles don’t interact that way

• alleles are simply variations in a gene’s nucleotide sequence– produces a different protein

• for any character- dominance/recessiveness relationships of alleles depend on the level at which we examine the phenotype

The Relation Between Dominance and Phenotype

• back to the round vs. wrinkled pea shape– when examined at the phenotypic level – Complete Dominance with round >

wrinkled • in heterozygotes – one dominant allele makes enough normal enzyme to prevent

wrinkling from happening– but at the biochemical level - Incomplete Dominance because in the

heterozygote - the amount of enzyme produced is somewhere between the dominant amount and the recessive amount


• Tay-Sachs disease is fatal; a dysfunctional enzyme causes an accumulation of lipids in the brain

– At the organismal level, the allele is recessive – disease only shows up if the genotype is homozygous recessive

– At the biochemical level, the alleles are incompletely dominant – the amount of lipid coating the neurons is intermediate between the normal individual and the affected individual • BUT no disease manifests itself• the enzyme level in a heterozygote is half the level of a normal

individual but still sufficient to produce a normal phenotype


Frequency of Dominant Alleles• dominant alleles are not necessarily more common in

populations than recessive alleles– for example, one baby out of 400 in the United States is born

with extra fingers or toes• the allele for this unusual trait is dominant to the allele for the

more common trait of five digits per appendage• in this example, the recessive allele is far more prevalent than the

population’s dominant allele– prevalence in the population initially determine via natural

selection

Multiple Alleles – Multi-Allelic Traits

• most genes exist in populations in more than two allelic forms– e.g. the four phenotypes of the ABO blood group in humans are determined

by three alleles for the enzyme (I) that attaches A or B carbohydrates to red blood cells: IA, IB, and i.

• the enzyme encoded by the IA allele adds the A carbohydrate, whereas the enzyme encoded by the IB allele adds the B carbohydrate; the enzyme encoded by the i allele adds neither – type O

Carbohydrate

Allele

(a) The three alleles for the ABO blood groups and their carbohydrates

(b) Blood group genotypes and phenotypes

Genotype

Red blood cellappearance

Phenotype(blood group)

A

A

B

B AB

none

O

IA IB i

iiIAIBIAIA or IAi IBIB or IBi

Pleiotropy

• most genes have multiple phenotypic effects• a property called pleiotropy

– e.g. pleiotropic alleles are responsible for the multiple symptoms of certain hereditary diseases - such as cystic fibrosis and sickle-cell disease

Extending Mendelian Genetics for Two or More Genes

• Some traits may be determined by two or more genes– Polygenic inheritance– Epistasis– Complementary

Polygenic Inheritance

Eggs

Sperm

Phenotypes:

Number ofdark-skin alleles: 0 1 2 3 4 5 6

1/81/8

1/81/8

1/81/8

1/81/8

1/8

1/8

1/8

1/8

1/8

1/8

1/8

1/8

1/646/64

15/6420/64

15/646/64

1/64

AaBbCc AaBbCc• Quantitative characters = those that vary in the population along a continuum

• quantitative variation usually indicates polygenic inheritance– an additive effect of two or more

genes on a single phenotype• skin color in humans is the best

example of polygenic inheritance

Epistasis• epistasis - a gene at one locus alters

the phenotypic expression of a gene at a second locus– e.g. Labrador retrievers and many

other mammals - coat color depends on two genes

– one gene determines the pigment color

• with alleles B for black melanin pigment and b for brown melanin pigment

– the other gene determines whether the pigment will be deposited in the hair

• with alleles E for pigment deposition and e for no pigment deposition

Sperm

Eggs

9 : 3 : 4

1/41/4

1/41/4

1/4

1/4

1/4

1/4

BbEe BbEe

BE

BE

bE

bE

Be

Be

be

be

BBEE BbEE BBEe BbEe

BbEE bbEE BbEe bbEe

BBEe BbEe BBee Bbee

BbEe bbEe Bbee bbee

Will produce a 9:3:4phenotypic ratio

• homozygous recessive ee is recessively epistatic to BB, Bb or bb genotypes “yellow lab”

Complementation

• when two chemical pathways are required to produce a phenotype

• e.g. sweet peas

• P AApp (white) x aabb(purple)• F1 AaBb (purple – unexpected)• F2 9 A– B— (purple)

3 A– bb (white)3 aa B— (white)1 aa bb (white)

• but it is a 9:7 purple: white phenotypic ratio

• notice the 9:3:3:1 Mendelian ratio is still there (independent assortment)

• two dominant alleles needed for purple flowers

• 2 enzymes, 2 chemical pathways that interact to produce the purple color

• both genes need to have dominant alleles

Nature and Nurture: The Environmental Impact on Phenotype

• another departure from Mendelian genetics arises when the phenotype for a character depends on environment as well as genotype

• norm of reaction is the phenotypic range of a genotype influenced by the environment– e.g. hydrangea flowers of the same genotype range from blue-violet

to pink – depend also on soil acidity in addition to their genotypes• norms of reaction are generally broadest for polygenic characters• such characters are called multi-factorial because genetic and

environmental factors collectively influence phenotype

An organism’s phenotype reflects its overall genotype and unique environmental history

Many human traits follow Mendelian patterns of inheritance

• Humans are not good subjects for genetic research

– Generation time is too long– Parents produce relatively few offspring– Breeding experiments are unacceptable

• However, basic Mendelian genetics endures as the foundation of human genetics

Pedigree Analysis• but the behavior of genes and their pattern of inheritance can

be studied in humans using a pedigree chart• a pedigree chart is a family tree that describes the

interrelationships of parents and children across generations• inheritance patterns of particular traits can be traced and

described using pedigrees• pedigrees can also be used to make predictions about future

offspring• we can use the multiplication and addition rules to predict the

probability of specific phenotypes within a pedigree chart

Pedigree Analysis - Symbols

Pedigree Analysis

• pedigree analysis often requires multiple generations to discern a pattern of inheritance

How to Analyze a Pedigree

• before assigning genotypes to the symbols – must determine if the trait is dominant or recessive

• then determine the genotype of each family member• with a recessive trait – fill the homozygote recessive individuals

first• with a dominant trait – fill the homozygote recessive individuals

first• the dominant genotypes in both types of charts will require more

investigation that may need several generations

• each generation has offspring with the affected trait• not absolute proof but should be a sign to investigate closer• fill in the unaffected individuals as homozygous recessive because you know their

genotype

Key

Male Female Affectedmale

Affected female

Mating Offspring

1stgeneration

2ndgeneration

3rdgeneration

Is a widow’s peak a dominant orrecessive trait?

(a)

Widow’speak

No widow’speak

WWor

Ww

Ww ww ww Ww

Ww Ww Wwww ww ww

ww

Dominantly Inherited Disorders

• Some human disorders are caused by dominant alleles• Dominant alleles that cause a lethal disease are rare and

arise by mutation• Achondroplasia is a form of dwarfism caused by a rare

dominant alleleParents

DwarfDd

Sperm

EggsDd

Dwarfdd

Normal

DdDwarf

ddNormal

D

d

d

d

Normaldd

• The timing of onset of a disease significantly affects its inheritance

• Huntington’s disease is a degenerative disease of the nervous system

• The disease has no obvious phenotypic effects until the individual is about 35 to 40 years of age

• Once the deterioration of the nervous system begins the condition is irreversible and fatal

Huntington’s Disease: A Late-Onset Lethal Disease

Is an attached earlobe a dominantor recessive trait?

b)

1stgeneration

2ndgeneration

3rdgeneration

Attachedearlobe

Freeearlobe

FForFf

Ff Ff Ff

Ff Ff

ff

ffffffFF or Ff

ff

• might skip a generation in the pedigree chart• BUT MIGHT NOT• 3rd generation:

– both parents are heterozygotes yet lack this trait– yet they have a child that is affected– pattern of inheritance supports the recessive allele theory

Recessively Inherited Disorders• many genetic disorders are inherited in a

recessive manner• these range from relatively mild to life-

threatening• recessively inherited disorders show up

only in individuals homozygous for the recessive allele

• Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal

– most individuals with recessive disorders are born to carrier parents

• e.g. albinism is a recessive condition characterized by a lack of pigmentation in skin and hair

Parents

NormalAa

Sperm

Eggs

NormalAa

AANormal

AaNormal(carrier)

AaNormal(carrier)

aaAlbino

A

A

a

a

Cystic Fibrosis (Mucoviscidosis)

• Cystic fibrosis is the most common lethal genetic disease in the United States– one out of every 2,500 people of European descent

• CFTR gene is an ABC gene that codes for a chloride transporter– loss of three nucleotides in CFTR (cystic fibrosis conductance regulator)– loss of phenylalanine at position 508 within the protein– diffusion of chloride ions out of epithelial cells is blocked– decreases the membrane potential – results in the diffusion of cations into

the cell– hypotonic environment outside the cell thickens the ECF and results in the

production of mucus outside the cell• symptoms include mucus buildup in some internal organs (blocks passages),

pancreatic damage (build up of digestive enzymes) and abnormal absorption of nutrients in the small intestine

• average life span in US – 37.4 yrs• average life span in Canada – 47.7 yrs 7q31.2

region 3band 1sub-band 2

Sickle-Cell Disease: A Genetic Disorder with Evolutionary Implications

• Sickle-cell disease affects one out of 400 African-Americans• caused by the substitution of a single amino acid in the hemoglobin protein in

red blood cells• homozygous individuals - all hemoglobin is abnormal (sickle-cell)• symptoms include physical weakness, pain, organ damage, and even paralysis• heterozygotes (said to have sickle-cell trait) are usually healthy but may suffer

some symptoms• about one out of ten African Americans has sickle cell trait, an unusually high

frequency of an allele with detrimental effects in homozygotes• Heterozygotes are less susceptible to the malaria parasite – heterozygous

advantage

• If a recessive allele that causes a disease is rare, then the chance of two carriers meeting and mating is low

• Consanguineous matings (i.e., matings between close relatives) increase the chance of mating between two carriers of the same rare allele

• most societies and cultures have laws or taboos against marriages between close relatives

Multi-factorial Disorders

• Many diseases, such as heart disease, diabetes, alcoholism, mental illnesses, and cancer have both genetic and environmental components

• Little is understood about the genetic contribution to most multifactorial diseases

Genetic Testing and Counseling

• Genetic counselors can provide information to prospective parents concerned about a family history for a specific disease

• Using family histories, genetic counselors help couples determine the odds that their children will have genetic disorders

• Probabilities are predicted on the most accurate information at the time; predicted probabilities may change as new information is available

• based on Mendelian genetics

Tests for Identifying Carriers

• For a growing number of diseases, tests are available that identify carriers and help define the odds more accurately

• In amniocentesis, the liquid that bathes the fetus is removed and tested• In chorionic villus sampling (CVS), a sample of the placenta is removed and tested• Other techniques, such as ultrasound and fetoscopy, allow fetal health to be

assessed visually in utero

(a) Amniocentesis (b) Chorionic villus sampling (CVS)

Ultrasound monitor

Amnioticfluidwithdrawn

FetusPlacentaUterus Cervix

Centrifugation

Fluid

Fetal cells

Several hours

Severalweeks

Several weeks

Biochemicaland genetic

tests

Karyotyping

Ultrasoundmonitor

Fetus

Placenta

Chorionic villi

Uterus

Cervix

Suctiontubeinsertedthroughcervix

Several hours

Fetal cells

Several hours

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2

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Newborn Screening

• Some genetic disorders can be detected at birth by simple tests that are now routinely performed in most hospitals in the United States

mendel and the gene idea

Documents