MENDELIAN GENETICS

What you will coverMENDELIAN GENETICSMENDELIAN GENETICSBasic Genetic Terminologies

Genotype, PhenotypeDominance, Recessive Genes, Alleles, LociHomozygous, Heterozygous, Diploid, etc

Mendelian LawsLaw of Segregation – Monohybrid Crosses, Punnett SquareLaw of Independent Assortment – Dihybrid Crosses, Trihybrid Crosses,

Partial Dominance, Backcross, TestcrossSex Chromosome

Sex Determination – Factorial calculationsSex Linkage – Reciprocal Crosses

Sex Linkage in HumansInfluence of Barr BodiesSex-influenced Traits, Sex-Limited Traits,

MODES OF INHERITANCEPEDIGREE ANALYSIS

PENETRANCE AND EXPRESSIVITYPLEIOTROPY

Recommended Reference1. Analysis and Principles of Genetics.

McGraw HillR. J. Brooker (2008)

2 A I t d ti t Q tit ti2. An Introduction to Quantitative Genetics4th Edition, Longman, gFalconer & McKay (1996)

We inherit 2 copies of genesBOA O BO

A or O B or O

Possibilities:AB, AO, BO, OO

Terminology

Gene• Controls a physical character of an individual• Inherited from parents via gametesInherited from parents via gametesAllele• Alternate forms of a geneAlternate forms of a gene

– eg components of blood group such as A, B, O. LocusLocus• Site of a specific gene or DNA sequence on a

chromosome

Terminology

GenotypeGenotype• Individual’s collection of genes• The allele combinations in an individual that causeThe allele combinations in an individual that cause

a particular trait or disorder.– For a diploid organism: eg blood group AA, AO, AB,etcp g g g p , , ,

Phenotype• Trait’s visible appearanceTrait s visible appearance

– Eg Eye colour, height,

• Physical expression of genotype (not visible)- a particular protein form, blood group

Terminology

Homozygote• Person having 2 identical alleles at a particular

locus on homologous chromosomes– Eg blood groups AA, BB, OO

Heterozygote• Person possessing different alleles at a• Person possessing different alleles at a

particular locus on homologous chromosomes– Eg blood groups AO, BO, ABg g p , ,

Hemizygote• Describes the genotype of males with an X-

linked trait, as males have only one X chromosome

Terminology

Dominant trait• An allele that is expressed when present in

even one copyEg blood group A, B

Recessive trait• An allele whose expression is masked by

th ll lanother allele

Terminology

Chromosome• A structure within a cell nucleus that carries genes.

A chromosome consists of a contiuous molecule of DNA and proteins wrapped around itDNA and proteins wrapped around it

Autosome• A non-sex-determining chromosome. Human has

22 pairs of autosomesSex Chromosome

A h t i i th t if• A chromosome containing genes that specify sex. Human male XY, female XX

(1) Mendel’s Laws(1) Mendel s Laws,(2) Sex Determination(2) Sex Determination

and Linkageand Linkage

GREGOR MENDEL (1822-1884)

- Monk in Augustinian Abbeyg y- Brno, Austro-Hungarian Empire

(now Brno, Czech Republic)- Entered monastery to be “free from

the bitter struggle for existence” (?)- Attended and intrigued by results of plant crossbreeding

in a course conducted by his AbbotL f d h & h i i U i f Vi- Left to study math & physics in Univ. of Vienna

- Returned 2 years later to conduct his own experiments with pea plantswith pea plants.

Experiments by Mendel

Experimental speciesGarden pea, Pisum sativum

1. Has well-defined characteristics2. Pure-bred (homozygous) varieties were available( yg )3. Flower hermaphroditic having male and female

parts. 4. Self fertilization ordinarily. Cross-fertilization4. Self fertilization ordinarily. Cross fertilization

possible5. Relatively short life cycle6 Large number of offspring produced from each6. Large number of offspring produced from each

mating.

F it ti EXPLAIN h it d tFavourite question: EXPLAIN why it was advantageous for Mendel to us the pea plant as an experimental model.

Fi 1 T itFig 1. Traits of the Garden Pea.

Klug & Cummins, pg 45

A Monohybrid Cross

P Tall x Short

F1 All tall (selfed)1 ( )

F2 Tall Short 2

(787) (277)

3 : 13 : 1

P :Parental generationF : First filial generationF1: First filial generationF2: Second filial generation

A Monohybrid Cross(B hi d th S )(Behind the Scene)

P Tall x ShortTT tt

Genes segregate in gamete-formation

P Gametes all T all tGametes fuse

F1 Tall x Tall

Tt (selfed) TtSegregation

(T t) (T t)(T t) (T t)Gametes fuse randomly

F2 TT Tt tT ttTall Short(787) (277)

3 : 1

Punnett Square

Male Gametes

T tT t

T TT Tt

t tT tt

Conclusions from the Monohybrid Cross

• Inheritance is not a process in which features of the 2 parents are blended together to produce an2 parents are blended together to produce an intermediate results– No medium height in F1

• Although F1 plants are tall, they must have received from their short parent a factor for shortness which remained ‘hidden’ in F1 and does not reveal itsremained hidden in F1 and does not reveal its presence in the outward appearance until F2.– No short plants in F1 but some appeared in F2

• Factor for tallness is dominant over factor for shortness, which is recessive– Factor for shortness must have been swamped by factor forFactor for shortness must have been swamped by factor for

tallness

Mendel’s First LawLaw of Segregation

The characteristics of an organism are controlled by genes occurring in pairs. Of a pair of such genes, only one can be carried in a single gamete

Table. Results of three Monohybrid Genetic Crosses carried out by Mendel (1)

Experiment 1P1 yellow pods × green pods F ll llF1 all yellowF2 428 yellow, 152 green (total 580)

Ratio 2.82 : 1 (ratio obtained by dividing 428 and 152 by 580)

Experiment 2P i l fl t i l flP1 axial flowers × terminal flowersF1 all axialF2 651 axial, 207 terminal (Ratio 3.13 : 1)

Experiment 3P1 inflated pods × constricted podsF1 all inflatedF2 882 inflated, 299 constricted (Ratio 2.95 : 1)

Monohybrid CrossPARTIAL DOMINANCE (Incomplete or semi-dominance)Every genotype has a distinguishable phenotypeThe heterozygote is intermediate between the twoThe heterozygote is intermediate between the two

homozygotes

Example: In snapdragons (flower colour)

P (cross) RR (Red) × rr (White)P (cross) RR (Red) × rr (White)

F ( lfi ) R ( i k)F1 (selfing) Rr (pink)

F2 phenotypic 1/4 RR : 1/2 Rr : 1/4 rr ratio 1 (Red) : 2 (Pink) : 1 (White)

A Dihybrid Cross

P Tall ShortColoured x White

F1 All tall, coloured (selfed)

F2 Tall Tall Short ShortColoured White Coloured White

9 : 3 : 3 : 1

Punnett Square

Male Gametes

TC Tc tC tc

TC TTCCTall, Colored

TTCcTall, Colored

TtCCTall, Colored

TtCcTall, Colored

Tc TTcCTall, Colored

TTccTall, white

TtcCTall, Colored

TtccTall, white

tC tTCCTall, Colored

tTCcTall, Colored

ttCCShort, Colored

ttCcShort, Colored

tc tTcC Tall, Colored

tTccTall, white

ttcC Short, Colored

ttcc Short, White

Mendel’s Second LawL f I d d t A t tLaw of Independent Assortment

Each member of a pair of alleles may combine randomly with either of another pair

Complete Dominance (Testing Phenotypes)G (yellow pod) : completely dominantG (yellow pod) : completely dominantg (green pod) : recessive

Phenotype : yellow greenGenotype : GG, Gg gg

1. Selfing or self-fertilizationOnly possible for self-fertilizing plants and i lanimals(a) homozygote (b) heterozygote

GG × GG Gg × GgGG × GG Gg × Gg

GG ¼GG : ½Gg : ¼ gg100% yellow 3 yellow : 1 green

Complete Dominance (Testing Phenotypes)2. Testcross

Backcross of individual to recessive parentortestcross to homozygous recessive tester stock

(a) homozygote (b) heterozygoteGG × gg Gg × ggGG gg Gg gg

Gg ½ Gg : ½ gg100% yellow 1 yellow : 1 green

Testcross

Tester stock is homozygous recessive for all gene loci

Monohybrid: Aa × aa

tester stockDihybrid: Aa Bb × aa bb

(homozygousrecessive)recessive)

Trihybrid: Aa Bb Cc × aa bb ccTrihybrid: Aa Bb Cc × aa bb cc

Relations among pairs of independent alleles gametes and F genotypes whenalleles, gametes, and F2 genotypes when

dominance is presentGardner, Simmons & Snustad, pg 33pg

No. of heterozygous

No. of kinds of gametes

No. of F2 genotypes

No. of F2 phenotypesheterozygous of gametes genotypes phenotypes

pairs 2n 3 n 2n 1 (Aa) 2 3 2

2 (A Bb) 4 9 4 2 (AaBb) 4 9 4 3 (AaBbCc) 8 27 8

4 16 81 16 4 16 81 16 10 1024 59,049 1024 n 2n 3 n 2n

Trihybrid Cross3 Gene Pairs, Complete Dominancep

Garden pea1. Seed shape : smooth (S) or wrinkled (s)2. Seed colour : yellow (Y) or green (y)2. Seed colour : yellow (Y) or green (y)3. Flower colour : red (A) or white (a)

P smooth, yellow, red × wrinkled, green,white, y , , g ,SS YY AA ss yy aa

F1 Ss Yy Aa

8 types of gametesSYA, SYa, SyA, sYA, Sya, sYa, syA, sya

Trihybrid Cross3 Pairs, Complete Dominance3 Pairs, Complete Dominance

F2 phenotypic ratioF2 phenotypic ratio

27/64 : 9/64 : 9/64 : 9/64 : 3/64 : 3/64 : 3/64 : 1/64

2 parentals8 phenotypes

6 recombinants

Sex Chromosomes• In normal mating approximately equal number of male

and female offspring are produced

sex ratio = No. of male offspring = approx. 1No of female offspringp g

• These results suggest the simplest hypothesis that sexis determined by a single pair of chromosomes calledthe sex chromosomes

• The other chromosomes are called autosomes• The other chromosomes are called autosomes• Genes on the sex chromosomes are called sex-linked

genes• Genes on the autosomes are called autosomal genes

Mechanisms of Sex Determination (examples)

1. XX-XY mechanisma) In man

The total number of chromosomes per cell is 23 pairs or 46• The total number of chromosomes per cell is 23 pairs or 46 chromosomes.

• 44 are autosomes and 2 are sex chromosomes.Female (homogametic) : XX + 44 autosomesMale (heterogametic) : XY + 44 autosomes

TDF (t ti d t i i f t th Y h )• TDF (testis determining factor on the Y-chromosome).• In humans the X-chromosome is larger than the Y-

chromosome• In mammals, the Y-chromosome determines the sex and is

required for maleness.

A

Fig 11. Photo of human chromosomes from a single nucleus at metaphase stage.

Male karyotype 22 pairs of autosomes1 pair of sex chromosmes B

(A) Metaphase spread of normal male chromosomes showing Q-banding

(B) K t f l h(B) Karyotype of normal human male, Q-banding

Mechanisms of Sex Determination b) In Drosophila• The total number of chromosomes is 4 pairs or 8chromosomes.

One pair of sex chromosomes & 3 pairs of autosomesOne pair of sex chromosomes & 3 pairs of autosomes.Female: XX + 3 pairs of autosomesMale: XY + 3 pairs of autosomes

• The Y-chromosome is J-shaped. Unlike mammals, in Drosophila the Y chromosome does not determine sex. It determines the fertility of malesfertility of males.

• Males are neither homozygotes or heterozygotes for genes on the sex chromosomes They are hemizygoussex chromosomes. They are hemizygous.

Mechanisms of Sex Determination 2. ZZ - ZW MECHANISM

Birds, moths, some fishesFemale : ZW (heterogametic)Male : ZZ (homogametic)

3. XX - XO MECHANISMF d i iFound in many insects

eg. grasshopper and the bug, ProtenorIn grasshopper:In grasshopper:

Female : XX + 22 autosomes (total 24 chr)Male: X + 22 autosomes (total 23 chr)

Mechanisms of Sex Determination ENVIRONMENT AND SEX DETERMINATION• In some invertebrates, sex determination is non-genetic.• Males and females have the• Males and females have thesame genotype but environmen-tal factors cause developmenti h hinto one sex or the other.

Example: Bonellia viridis,a marine worm

Fig 12. Gardner, Simmons & Snustad,page 77.p g

QuestionOther factors being equal, what are the chances of a newly wed having a baby girl or of having a baby boy for their first child? And Why Whatbaby boy for their first child? And Why. What are the chances of having a baby girl or of having a baby boy for their second child? And Why as wellWhy as well

50%:50%, because to have a girl, the chromosome of the child gneeds to be XX (one each from each parent) while to have a boy, the chromosome of the child needs to be XY (X from mother while Y from father). The chance of the Y chromosome segregating into the ) g g gchild from the father (who is XY as well) is 50% (i.e., the father either segregates an X or a Y chromosome). The chances of having a baby girl or boy remains 50%:50% for the second (or anyhaving a baby girl or boy remains 50%:50% for the second (or any consecutive child), for the same reason.

If the couple has 3 child Chance of having all boys?

Factorial CalculationsIf the couple has 3 child. Chance of having all boys?

½ x ½ x ½ = 1/8or

P = (n!/ x!y!)pxqy

where

n = total number of individual

x = number of individuals in one class

y = number of individuals in the other class

p = probability of falling into the class with x individuals

q = probability of falling into the class with y individuals

P = (3!/3!0!)(½)3(½)0

= (½)3 = 1/8

Sex Linkage• Genes on autosomes are called autosomal genes• Genes on sex chromosomes are sex-linked genes• In Drosophila and man, where the males are

heterogametic, most sex-linked genes are located on the X-chromosome

• These genes are X-linked• The Y chromosome is essentially devoid of genes• Few animals carry some genes on the Y-chromosome

that has visible effects• Such Y-linked or holandric genes are transmitted from

father to son and never appear in females

How do we test for sex linkage?

Reciprocal crosses

• Gives identical results in the F1 and F2 generations for autosomal genes

• Gives different results in the F1 and F2 generations for sex-linked (X-linked) genes( ) g

• All of Mendel’s experiments involved only autosomal genesgenes

Reciprocal crosses

Example:Example:Reciprocal crosses between the white-eye flies with red eye flies examineeye flies with red-eye flies, examine phenotypes of the F1 and F2 generations:

F l d M l hiFemale red-eye × Male white-eyeFemale white-eye × Male red-eye

Sex-linkage in Drosophila

Parent gengen.

white-eye, w: red eye gene, w+

Cross between red-eye female with white-eye male.

F1 gen.1 g

Brooker, Fig 3.5, pg 55.

F1 gen.1 g

F2 gen.

B k FiBrooker, Fig 3.5, pg 55.

Sex-linkage in Drosophila

ParentParent gen. white-eye, w: red eye, w+.

Cross between white-eye female with red-eye male.

F genF1 gen.

Brooker, Fig 3.6, pg 56

Sex-linkage in Drosophila

F1 gen.1 ge

white-eye,w: red eye, w+

Cross between white-eye

F2 gen.

female with red-eye male.

2 g

Brooker, Fig 3.6, pg 56

Example: Sex Linkage in HumansRed-green colour blindness is due to a recessive gene. The allele for normal vision is dominant

C = normal vision; c = red-green colour blindness

Females:XC XC - dominant homozygote (normal vision) XC Xc - heterozygote, (carrier) normal visionXc Xc - recessive homozygote (colourX X recessive homozygote (colour

blindness)

Males: XCY - normal visionMales: X Y normal visionXcY - red-green colour blindness

Sex Linkage in Humans

Expression of single sex-linked recessive genes inhemizygous males explain the higher incidencehemizygous males explain the higher incidenceof sex-linked disorders in males than females.

Example: Caucasian males - 8% colour blindCaucasian females - 1% colour blindCaucasian females - 1% colour blind

Other sex linked disorders are haemophilaOther sex-linked disorders are haemophila,G-6PD deficiency etc

Sex Linkage in Humans

Reciprocal matings: Colour blindnessfemale male female malenormal × c.b. c.b. × normalXC XC XcY Xc Xc XCYXC XC XcY Xc Xc XCY

½ XC Xc : ½ XCY ½ XC Xc : ½ XcYdaughters sons daughters sons

l l l bnormal normal normal c.b.(carrier) (carrier)

Shows criss-cross pattern of inheritance

Sex Chromatin Body – Barr body? (M. L. Barr)( )

Present in:

1 Nerve cells of female cats the chromatin body is dark spot1. Nerve cells of female cats - the chromatin body is dark spot in the nucleus revealed by DNA stainingNot present in nerve cells of male cats

2 Epithelial cells of buccal mucosa of females in2. Epithelial cells of buccal mucosa of females inhumans.

What is a sex chromatin body? yHeterochromatic body (X-chromosome) found inThe nuclei of normal female mammals. Absent in males.

Use of the sex chromatin body to differentiate betweenMales and females in humans.

Sex chromatin body = Barr bodyy y

Nucleus of cellsNucleus of cells of human epidermis ill t ti thillustrating the sex chromatin bodies or Barr bodies in females

Fig 19. Gardner,Fig 19. Gardner, Simmons & Snustad, page 78.

Nuclei of cells with different number of Barr bodies. Hartl, pg 141a bod es a t , pg

One X chromosome = female Turner’s Syndrome (no Barr body)Two X chromosomes = normal female (one Barr body)( y)Three Xs chromosomes = Superfemale (2 Barr bodies)Four Xs chromosomes = Superfemale (3 Barr bodies)

(a) (b) (c) (d)57

Sex-Influenced DominanceThe dominance of alleles differs in the heterozygotes of the two sexes.

Affected by sex hormones

Example: in sheepb+ = horned b = hornlessb horned b hornless

PHENOTYPEGENOTYPES MALES FEMALESGENOTYPES MALES FEMALES

b+b+ horned horned b+b horned hornlessb b h l h lb b hornless hornless

Sex-Influenced TraitAutosomal gene with traits expressed in one of the sexes, either because of internal hormones environment or anatomical dissimilaritiesenvironment or anatomical dissimilarities.

e g Bulls have genes for milk production that may bee.g., Bulls have genes for milk production that may be transmitted to daughters, but their sons are unable to express this trait.

Another example of sex influenced trait: in manPattern Baldness b+ = bald b = non-bald

PHENOTYPEPHENOTYPEGENOTYPES MALES FEMALES

b+b+ bald bald b+b bald non-baldb b non-bald non-bald

Sex-Influenced TraitQ i L ’ id i fl d i i l lQuestion: Let’s consider two sex-influenced traits simultaneously, pattern baldness and short index finger, both of which are dominant in men and recessive in women.

A heterozygous bald man with long index finger marries a heterozygous long-fingered “bald-prone” womanheterozygous long-fingered, bald-prone woman.

Determine the phenotypic expectation of their children.Genotype Male Female Genotype Male Female

B1B1 Bald Bald F1F1 Short- Short-fingered fingered

B1B2 Bald Non-bald F1F2 Short-fingered

Long-fingeredfingered fingered

B2B2 Non-bald Non-bald F2F2 Long-fingered

Long-fingered

Sex-Influenced TraitP: B1B2, F2F2 x B1B1, F1F2

bald, long-fingered man bald-prone, long fingered womeng g p g g

F1: 1/2 F1F2 = 1/4 B1B1, F1F2

1/2 B1B1bald, short (men) / bald, long (women)

1/2 F2F2 = 1/4 B1B1, F2F2Dichotomous

branching bald, long (men) / bald, long (women)

1/2 F1F2 = 1/4 B1B2, F1F2

1 2

gsystem

bald, short (men) / non-bald, long (women)

1/2 B1B2

1/2 F2F2 = 1/4 B1B2, F2F2

bald long (men) / non-bald long (women)bald, long (men) / non-bald, long (women)

F1 summary: Men: 1/2 bald, short-fingered : 1/2 bald, long fingered

Women: 1/2 bald, long-fingered : 1/2 non-bald, long fingered

Sex-limited Traits• Traits that occur in only one of the two sexes

• For example in humans• For example in humans– Breast development is normally limited to females

Beard growth is normally limited to males– Beard growth is normally limited to males

• Another (textbook) example: Feather plumage in chicken– Caused by an autosomal gene

H f th i i t ll d b d i t ll l– Hen-feathering is controlled by a dominant allele expressed in both sexes

– Cock-feathering is controlled by a recessive allele onlyCock feathering is controlled by a recessive allele only expressed in males

Sex-limited Traits• The pattern of hen-feathering depends on the

production of sex hormones

• If the single ovary is surgically removed from a newly hatched hh female– She will develop cock-feathering and look

indistinguishable from a male

Genotype Phenotype in Females

Phenotype in Males

hh hen-feathered cock-feathered

Hh hen-feathered hen-feathered

HH hen-feathered hen-feathered

QuestionSometimes an animal, possibly even humans, has eyes of two different colors. Another example is the calico cat with fur that comes in patches of different pcolors (black and/or orange). Why isn’t the fur of the calico uniform black or white or orange? What is a possible explanation for this trait.p p

The various colour patches (or eye colour) arose from cells early in development that expresses either a gene for one or the other colour. In the case of the calico cat, the trait for fur colour is carried on the X chromosome. Incase of the calico cat, the trait for fur colour is carried on the X chromosome. In female mammals however, one of the X chromosome is inactivated, forming a condensed mass, called a Barr body. Thus, the nuclei of a normal XX female will have one barr body and the other the ‘active’ X chromosome. Which X ychromosome is activated or becomes a barr body is entirely random. Thus, in a calico cat (usually only in females), the X chromosome carries the gene for either black or orange in either one of the chromosome. The inactivation of one of these in a particular cell makes it produce the colour trait of the other active chromosome. This mosaic formation is a result of the early activation or deactivation of genes sitting on a particular chromosome.

What about the white patches?Notice the white patches on the legs and the frontal

The white patches in tortie-and-white (tricolour, calico) cats is caused

Notice the white patches on the legs and the frontal sides of the cat mostly.

p ( , )by the piebald spotting gene.

This is a semi-dominant gene (with very variable expression ranging from nearly all white to nearly all coloured with only a few white hairs).

This gene affects the embryo cells which will become pigment-producing ki llskin cells.

These cells are initially formed along the "neural crest" - the embryo's backbone area and migrate to all over the body during formation of thebackbone area - and migrate to all over the body during formation of the skin.

Where these pigment producing cells fail to get in position before the skin is fully formed, there will be areas of skin which lack pigment producing cells i.e. y , p g p gwhite areas.

White areas are usually the areas furthest from the cat's backbone - paws, belly, chest and chin - these areas take longest to reach.

Single-gene DisordersSingle-gene Disorders

• aka Mendelian disorders

• Mutation in single gene• Mutation in single gene

• Well characterized genetic etiology

• Usually very rare

• Examples: Thalassaemia Duchene• Examples: Thalassaemia, Duchene Muscular Distrophy, haemophilia

Modes of InheritanceModes of InheritanceMendelian Non-Mendelian

• Autosomal dominant • Maternal Inheritance

• Autosomal recessive

• X-linked dominant

• Complex inheritance (linkage)

• X-linked dominant

• X-linked recessive• Uniparental disomy

• Y-linked

Modes of InheritanceModes of Inheritance

Autosomal dominant

Th i h it tt f d i t• The inheritance pattern of a dominant allele on an autosome.

• Phenotypes can affect both males and females

• Does not skip generations

Modes of InheritanceModes of Inheritance

Autosomal recessive

Th i h it tt f i• The inheritance pattern of a recessive allele on an autosome.

• Phenotypes can affect both males and females

• Can skip generations

Modes of InheritanceModes of Inheritance

X linked dominantX-linked dominant • Affects hemizygous males and heterozygous

femalesfemales• Excess of affected females

Vit D i t t i k t• e.g. Vit D resistant rickets• In some conditions, the disorder is lethal in

hemizygous males In this case fewer maleshemizygous males. In this case, fewer males in family, all healthy, excess of females, half affected

XX Female XY Male

Modes of InheritanceX-linked Dominant

Congenital Generalised Hypertrichosis (CGH)“ape man”

Modes of InheritanceModes of InheritanceX-linked recessive

• Both males and females can be affected

• Manifest in the female only when recessive yallele is in double dose (homozygous state)

• In male, mutant allele is always manifested , ysince there is no normal allele to counteract the effect

• Transmitted by affected males and healthy female carriers

• e.g. colour blindness, haemophilia A, B

Modes of InheritanceModes of Inheritance

Y-linked (Holandric Inheritance)

• Only males are affectedOnly males are affected

• Affected male transmits the trait to all his sons but to none of his daughters

• e g hairy earse.g. hairy ears

Pedigree Analysis• A Pedigree is a diagram of family relationships

symbols to represent peoplelines to represent genetic relationshipsoften used to determine the mode of inheritance ofgenetic disease

• The term “pedigree” arose in the 15th centuryThe term pedigree arose in the 15 century.French word “pie de grue” “crane’s foot”

Pedigree Analysis Why bother?• In human, critically informative mating cannot be made by design

human geneticists have to rely on pre-existing information in

Pedigree Analysis – Why bother?

human geneticists have to rely on pre existing information infamily history.

- Families are tools, the bigger the family the better

• Also useful for studying traits in organisms in which breeding couldnot be carried out (Eg., long life cycles, huge body size, unable tobreed in captivity, and etc.)

Pedigree - Example

Pedigree - Example

A l diAn unusual pedigree

• A partial pedigree of Egypt’s Pt l d tPtolemy dynasty.

• Shows only genealogy, no traits.

•It is ladder-like because of extensive inbreeding.

(Ref: Lewis R. 2007. Human Genetics. Concepts and Applications. 7th Ed. McGraw-Hill)

Pedigree Symbolsg y

/ Carrier

Question

Study the following pedigree. Deduce the method of inheritance and the genotype of the relevant individuals.and the genotype of the relevant individuals.

Question

Study the following pedigree. Deduce the method of inheritance and the genotype of the relevant individuals.and the genotype of the relevant individuals.

I

II

III

1 2 3 4

1 2

IV21

Penetrance and Expressivity

PenetranceThe proportion of genotype that express a trait, even if mildlytrait, even if mildly

ExpressivityVariation in severity/intensity in differentVariation in severity/intensity in different individuals of a particular genotype.

Penetrance and ExpressivityExample of trait displaying both incomplete penetrance and expressivity:incomplete penetrance and expressivity:

Polydactyly (extra fingers,toes)– Dominant allele– Some with the allele have normal

number of fingers and toes– Some with polydactyly have an extra digit on both p y y y g

hands and a foot, some have 2 extra digits on both hands and both feet, some may have only 1 extra digit on finger

Pleiotropy• A gene with multiple effects, different subsets of

which may occur in different individuals• Example: sickle cell gene causes the syndrome called

‘sickle cell anaemia’– The effects include: abnormal haemoglobin sickle-– The effects include: abnormal haemoglobin, sickle-

shaped red blood cells with tendency to clump and clog in small blood vessels. This result in heart, kidney liver spleen and brain damagekidney, liver, spleen and brain damage.

Normal red blood cells

Normal red blood cells Sickle-shapedred blood cells

Pleiotropic Effects

Mutant Gene

The sickle cell gene

Abnormal β-polypeptide

- Gut → Abdominal pain- Spleen → Splenic infarction- Extremities → Limb pain

→ Bone tendernessβ polypeptide in HbS Ischaemia

→ Thrombosis →Infarction

viscosity & clumping of cells

→ Bone tenderness→ “Rheumatism”→ Osteomyelitis

- Brain → Cerebrovascular accident

Low solubility of reduced HbS → Sickling

- Kidney → Haematuria→ Renal Failure

- Lung → “Pneumonia”Heart → Heart failure

→ AnaemiaDestruction of sickle cells

- Heart → Heart failure

- Splenomegaly- Weakness- Lassitude- Abnormal skull radiographs

What you are expected to know by nowMENDELIAN GENETICSMENDELIAN GENETICSBasic Genetic Terminologies

Genotype, PhenotypeDominance, Recessive Genes, Alleles, LociHomozygous, Heterozygous, Diploid, etc

Mendelian LawsLaw of Segregation – Monohybrid Crosses, Punnett SquareLaw of Independent Assortment – Dihybrid Crosses, Trihybrid Crosses,

Partial Dominance, Backcross, TestcrossSex Chromosome

Sex Determination – Factorial calculationsSex Linkage – Reciprocal Crosses

Sex Linkage in HumansInfluence of Barr BodiesSex-influenced Traits, Sex-Limited Traits,

MODES OF INHERITANCEPEDIGREE ANALYSIS

PENETRANCE AND EXPRESSIVITYPLEIOTROPY