MENDELIAN GENETICS

What you will cover

MENDELIAN GENETICS Basic Genetic Terminologies
Genotype, Phenotype Dominance, Recessive Genes, Alleles, Loci Homozygous, Heterozygous, Diploid, etc

Mendelian Laws
Law of Segregation Monohybrid Crosses, Punnett Square Law of Independent Assortment Dihybrid Crosses, Trihybrid Crosses, Partial Dominance, Backcross, Testcross

Sex Chromosome
Sex Determination Factorial calculations Sex Linkage Reciprocal Crosses Sex Linkage in Humans Influence of Barr Bodies Sex-influenced Traits, , Sex-Limited Traits

MODES OF INHERITANCE PEDIGREE ANALYSIS PENETRANCE AND EXPRESSIVITY PLEIOTROPY

Recommended Reference
1. Analysis and Principles of Genetics.
McGraw Hill

R. J. Brooker (2008)

2 A 2. An I Introduction t d ti to t Quantitative Q tit ti Genetics

4th Edition, , Longman g

Falconer & McKay (1996)

We inherit 2 copies of genes

AO A or O BO B or O

Possibilities: AB, AO, BO, OO

Terminology
Gene Controls a physical character of an individual Inherited from parents via gametes Allele Alternate forms of a gene
eg components of blood group such as A, B, O.

Locus Site of a specific gene or DNA sequence on a chromosome

Terminology
Genotype Individuals collection of genes The allele combinations in an individual that cause a particular trait or disorder.
For a diploid p organism: g eg g blood g group p AA, , AO, , AB,etc ,

Phenotype Traits s visible appearance Trait

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 particular locus on homologous chromosomes

Eg g blood g groups p AO, , BO, , AB

Hemizygote Describes the genotype of males with an Xlinked trait, as males have only one X chromosome

Terminology
Dominant trait An allele that is expressed when present in even one copy
Eg blood group A, B

Recessive trait An allele whose expression is masked by another th allele ll l

Terminology
Chromosome A structure within a cell nucleus that carries genes. A chromosome consists of a contiuous molecule of DNA and proteins wrapped around it Autosome A non-sex-determining chromosome. Human has 22 pairs of autosomes Sex Chromosome A chromosome h containing t i i genes th that t specify if sex. Human male XY, female XX

(1) Mendels Mendel s Laws Laws, (2) Sex Determination and Linkage

GREGOR MENDEL (1822-1884)

- Monk in Augustinian g Abbey 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 Abbot - Left L f to study d math h & physics h i in i U Univ. i of f Vi Vienna - Returned 2 years later to conduct his own experiments with pea plants plants.

Experiments by Mendel
Experimental species Garden pea, Pisum sativum 1. Has well-defined characteristics 2. Pure-bred ( (homozygous) yg ) varieties were available 3. Flower hermaphroditic having male and female parts. 4. Self fertilization ordinarily. Cross-fertilization Cross fertilization possible 5. Relatively short life cycle 6 Large number of offspring produced from each 6. mating.
Favourite F it question: ti EXPLAIN why h it was advantageous d t for Mendel to us the pea plant as an experimental model.

Fig 1. Fi 1 Traits T it of the Garden Pea.

Klug & Cummins, pg 45

A Monohybrid Cross
P F1 F2 Tall x Short

All tall ( (selfed) ) Tall

(787)

Short
(277)

3
P :Parental generation F1: First filial generation F2: Second filial generation

A Monohybrid Cross
(B hi d th (Behind the S Scene) )
P Tall TT x Short tt all t x
(selfed) Segregation Genes segregate in gamete-formation

P Gametes all T
Gametes fuse

F1

Tall Tt (T

Tall Tt t) tT : tt Short
(277)

t) TT Tt Tall

(T

Gametes fuse randomly

F2

(787)

Punnett Square
Male Gametes

T T TT

t Tt

tT

tt

Conclusions from the Monohybrid Cross

Inheritance is not a process in which features of the 2 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 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 for tallness

Mendels First Law

Law 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 1
P1 yellow pods green pods F1 all ll yellow ll F2 428 yellow, 152 green (total 580) Ratio 2.82 : 1 (ratio obtained by dividing 428 and 152 by 580)

Experiment 2
P1 axial i l flowers fl terminal t i l flowers fl F1 all axial F2 651 axial, 207 terminal (Ratio 3.13 : 1)

Experiment 3
P1 inflated pods constricted pods F1 all inflated F2 882 inflated, 299 constricted (Ratio 2.95 : 1)

Monohybrid Cross
PARTIAL DOMINANCE (Incomplete or semi-dominance) Every genotype has a distinguishable phenotype The heterozygote is intermediate between the two homozygotes
Example: In snapdragons (flower colour) P (cross) RR (Red)

rr (White)

F1 (selfing) ( lfi )

R (pink) Rr ( i k)

F2 phenotypic ratio

1/4 RR 1 (Red)

: 1/2 Rr : 2 (Pink)

: 1/4 rr : 1 (White)

A Dihybrid Cross
P Tall Coloured Short White

F1 F2

All tall, coloured (selfed) Tall Tall Coloured White 9 : 3 : Short Short Coloured White 3 : 1

Punnett Square
Male Gametes

TC TC Tc tC tc
Tall, Colored

Tc
Tall, Colored

tC TtCC
Tall, Colored

tc TtCc
Tall, Colored

TTCC TTCc TTcC

Tall, Colored

TTcc
Tall, white

TtcC
Tall, Colored

Ttcc
Tall, white

tTCC
Tall, Colored

tTCc
Tall, Colored

ttCC
Short, Colored

ttCc
Short, Colored

tTcC Tall,
Colored

tTcc
Tall, white

ttcC
Short, Colored

ttcc
Short, White

Mendels Second Law

L Law of f Independent I d d t Assortment A t t Each member of a pair of alleles may combine randomly with either of another pair

Complete Dominance (Testing Phenotypes)

G (yellow pod) : completely dominant g (green pod) : recessive Phenotype : Genotype : yellow GG, Gg green gg

1. Selfing or self-fertilization
Only possible for self-fertilizing plants and animals i l (a) homozygote (b) heterozygote GG GG Gg Gg

GG 100% yellow

GG : Gg : gg 3 yellow : 1 green

Complete Dominance (Testing Phenotypes)

2. Testcross Backcross of individual to recessive parent or testcross to homozygous recessive tester stock (a) homozygote GG gg (b) heterozygote Gg gg

Gg 100% yellow

Gg : gg 1 yellow : 1 green

Testcross
Tester stock is homozygous recessive for all gene loci Monohybrid: Aa aa tester stock Dihybrid: Aa Bb aa bb (homozygous recessive) Trihybrid: Aa Bb Cc aa bb cc

Relations among pairs of independent alleles gametes alleles, gametes, and F2 genotypes when dominance is present
Gardner, Simmons & Snustad, pg 33

No. of heterozygous pairs 1 (Aa) 2 (A (AaBb) Bb) 3 (AaBbCc) 4 10 n

No. of kinds No. of F2 of gametes genotypes 2n 3n 2 3 4 9 8 27 16 81 1024 59,049 2n 3n

No. of F2 phenotypes 2n 2 4 8 16 1024 2n

Trihybrid Cross 3 Gene Pairs, Complete p Dominance

Garden pea 1. Seed shape : smooth (S) or wrinkled (s) 2. Seed colour : yellow (Y) or green (y) 3. Flower colour : red (A) or white (a)

smooth, , yellow, y , red SS YY AA

wrinkled, , green,white g , ss yy aa

F1

Ss Yy Aa

8 types of gametes SYA, SYa, SyA, sYA, Sya, sYa, syA, sya

Trihybrid Cross 3 Pairs, Complete Dominance

F2 phenotypic ratio
27/64 : 9/64 : 9/64 : 9/64 : 3/64 : 3/64 : 3/64 : 1/64 2 parentals 8 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. 1 No of female offspring p g These results suggest the simplest hypothesis that sex is determined by a single pair of chromosomes called the sex chromosomes 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 mechanism a) In man 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 autosomes Male (heterogametic) : XY + 44 autosomes

TDF (testis (t ti determining d t i i factor f t on the th Y-chromosome Y h ) ). In humans the X-chromosome is larger than the Ychromosome 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 autosomes 1 pair of sex chromosmes

(A) Metaphase spread of normal male chromosomes showing Q-banding (B) Karyotype K t of f normal l human h 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 autosomes. autosomes Female: XX + 3 pairs of autosomes Male: 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 males males.

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

Mechanisms of Sex Determination

2. ZZ - ZW MECHANISM Birds, moths, some fishes
Female : ZW (heterogametic) Male : ZZ (homogametic)

3. XX - XO MECHANISM
Found F d in i many insects i eg. grasshopper and the bug, In grasshopper: Protenor

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 same genotype but environmental factors cause development i into one sex or the h other. h Example: Bonellia viridis, a marine worm
Fig 12. Gardner, Simmons & Snustad, page p g 77.

Question
Other 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 Why. What are the chances of having a baby girl or of having a baby boy for their second child? And Why as well 50%:50%, because to have a g girl, the chromosome of the child needs 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 g g g into the child 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 any consecutive child), for the same reason.

Factorial Calculations
If the couple has 3 child. child Chance of having all boys?
x x = 1/8 or 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!)()3()0 = ()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) g genes All of Mendels experiments involved only autosomal genes

Reciprocal crosses
Example: Reciprocal crosses between the whiteeye flies with red-eye red eye flies flies, examine phenotypes of the F1 and F2 generations:
Female F l red-eye d Male M l white-eye hi Female white-eye Male red-eye

Sex-linkage in Drosophila
Parent gen. gen
white-eye, w: red eye gene, w+

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

F1 g gen.

Brooker, Fig 3.5, pg 55.

F1 g gen.

F2 gen.

Brooker, B k Fi Fig 3.5, pg 55.

Sex-linkage in Drosophila

Parent gen.

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

Cross between whiteeye female with redeye male.

F1 gen. gen

Brooker, Fig 3.6, pg 56

Sex-linkage in Drosophila

F1 ge gen.

white-eye,w: red eye, w+

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

F2 g gen.

Brooker, Fig 3.6, pg 56

Example: Sex Linkage in Humans

Red-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 vision Xc Xc - recessive homozygote (colour blindness) Males: XCY - normal vision XcY - red-green colour blindness

Sex Linkage in Humans

Expression of single sex-linked recessive genes in hemizygous males explain the higher incidence of sex-linked disorders in males than females. Example: Caucasian males - 8% colour blind Caucasian females - 1% colour blind Other sex-linked sex linked disorders are haemophila, haemophila G-6PD deficiency etc

Sex Linkage in Humans

Reciprocal matings: Colour blindness female male female male normal c.b. c.b. normal XC XC XcY Xc Xc XCY

XC X c : XC Y daughters sons normal l normal l (carrier)

XC X c : daughters normal l (carrier)

XcY sons c.b. b

Shows criss-cross pattern of inheritance

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

Present in: 1 1. Nerve cells of female cats - the chromatin body is dark spot in the nucleus revealed by DNA staining Not present in nerve cells of male cats 2 Epithelial cells of buccal mucosa of females in 2. humans. What is a sex chromatin body? y Heterochromatic body (X-chromosome) found in The nuclei of normal female mammals. Absent in males. Use of the sex chromatin body to differentiate between Males and females in humans. Sex chromatin body y = Barr body y

Nucleus of cells of human epidermis ill t ti the illustrating th sex chromatin bodies or Barr bodies in females
Fig 19. Gardner, Simmons & Snustad, page 78.

Nuclei of cells with different number of Barr a bod bodies. es Hartl, a t , pg 141
One X chromosome = female Turners Syndrome (no Barr body) (one Barr body) y) Two X chromosomes = normal female ( Three Xs chromosomes = Superfemale (2 Barr bodies) Four Xs chromosomes = Superfemale (3 Barr bodies)

(a)
57

(b)

(c)

(d)

Sex-Influenced Dominance
The dominance of alleles differs in the heterozygotes of the two sexes. Affected by sex hormones Example: in sheep b+ = horned b = hornless
GENOTYPES b+b+ b+b bb PHENOTYPE MALES FEMALES horned horned horned hornless h hornless l hornless h l

Sex-Influenced Trait
Autosomal gene with traits expressed in one of the sexes, either because of internal hormones environment or anatomical dissimilarities. dissimilarities e.g., e 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 man Pattern Baldness b+ = bald b = non-bald PHENOTYPE GENOTYPES MALES FEMALES b+b+ bald bald b+b bald non-bald bb non-bald non-bald

Sex-Influenced Trait
Question: Q i L consider Lets id two sex-influenced i fl d traits i simultaneously, i l l 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 long-fingered, bald-prone bald-prone woman. woman Determine the phenotypic expectation of their children.
Genotype B1B1 B1B2 B2B2 Male Bald Bald Non-bald Female Bald Non-bald Non-bald Genotype F1F1 F1F2 F2F2 Male Shortfingered Shortfingered Longfingered Female Shortfingered Longfingered Longfingered

Sex-Influenced Trait
P: B1B2, F2F2 bald, long-fingered g g man F1: 1/2
Dichotomous branching g system

B1B1, F1F2 bald-prone, p long g fingered g women

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

1/2 F1F2 = 1/4 B1B1, F1F2 B1 B1

1/2 F2F2 = 1/4 B1B1, F2F2

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

1/2 F1F2 = 1/4 B1B2, F1F2

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

1/2 B1B2 1/2 F2F2 = 1/4 B1B2, F2F2

bald long (men) / non-bald bald, 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
Breast development is normally limited to females Beard growth is normally limited to males Another (textbook) example: Feather plumage in chicken
Caused by an autosomal gene Hen-feathering H f th i i is controlled t ll d b by a d dominant i t allele ll l expressed in both sexes Cock Cock-feathering 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 hh Hh HH Phenotype in Females hen-feathered hen-feathered hen-feathered Phenotype in Males cock-feathered hen-feathered hen-feathered

Question
Sometimes an animal, possibly even humans, has eyes of two different colors. Another example is the calico cat with fur that comes in p patches of different colors (black and/or orange). Why isnt the fur of the calico uniform black or white or orange? What is a possible explanation p p for this trait.
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. 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 y and the other the active X chromosome. Which X chromosome 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 sides of the cat mostly.

The white p patches in tortie-and-white ( (tricolour, , calico) ) cats is caused 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 skin ki cells. ll These cells are initially formed along the "neural crest" - the embryo's backbone 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
y formed, , there will be areas of skin which lack pigment pg p producing g cells i.e. fully white 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 Disorders
aka Mendelian disorders Mutation in single gene Well characterized genetic etiology Usually very rare Examples: Thalassaemia, Thalassaemia Duchene Muscular Distrophy, haemophilia

Modes of Inheritance
Mendelian Autosomal dominant Autosomal recessive X-linked dominant Uniparental disomy X-linked recessive Y-linked Non-Mendelian Maternal Inheritance Complex inheritance (linkage)

Modes of Inheritance
Autosomal dominant Th The i inheritance h it pattern tt of f a dominant d i t allele on an autosome. Phenotypes can affect both males and females Does not skip generations

Modes of Inheritance
Autosomal recessive Th The i inheritance h it pattern tt of f a recessive i allele on an autosome. Phenotypes can affect both males and females Can skip generations

Modes of Inheritance
X linked dominant X-linked Affects hemizygous males and heterozygous females Excess of affected females e.g. Vit D resistant i t t rickets i k t In some conditions, the disorder is lethal in hemizygous males males. In this case case, fewer males in family, all healthy, excess of females, half affected XX Female XY Male

Modes of Inheritance
X-linked Dominant
Congenital Generalised Hypertrichosis (CGH) ape man

Modes of Inheritance
X-linked recessive Both males and females can be affected Manifest in the female only y when recessive allele is in double dose (homozygous state) In male, , mutant allele is always y manifested since 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 Inheritance
Y-linked (Holandric Inheritance) Only males are affected Affected male transmits the trait to all his sons but to none of his daughters e.g. e g hairy ears

Pedigree Analysis
A Pedigree is a diagram of family relationships symbols to represent people lines to represent genetic relationships often used to determine the mode of inheritance of genetic disease The term pedigree pedigree arose in the 15th century. century French word pie de grue cranes foot

Pedigree Analysis Why bother?

In human, critically informative mating cannot be made by design human geneticists have to rely on pre pre-existing existing information in family history. - Families are tools, the bigger the family the better Also useful for studying traits in organisms in which breeding could not be carried out (Eg., long life cycles, huge body size, unable to breed in captivity, and etc.)

Pedigree - Example

Pedigree - Example

A unusual An l pedigree di A partial pedigree of Egypts Pt l Ptolemy dynasty. d t 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 g Symbols y

/ Carrier

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

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

I II
1 2 3 4

III IV

Penetrance and Expressivity

Penetrance
The proportion of genotype that express a trait, even if mildly

Expressivity
Variation in severity/intensity in different individuals of a particular genotype.

Penetrance and Expressivity

Example of trait displaying both incomplete penetrance and expressivity:
Polydactyly (extra fingers,toes)
Dominant allele Some with the allele have normal number of fingers and toes Some with p polydactyly y y y have an extra digit g on both 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, haemoglobin sickleshaped red blood cells with tendency to clump and clog in small blood vessels. This result in heart, kidney liver kidney, liver, spleen and brain damage damage.
Normal red blood cells

Normal red blood cells

Sickle-shaped red blood cells

Pleiotropic Effects
The sickle cell gene
Mutant Gene Abnormal -polypeptide polypeptide in HbS - Gut Abdominal pain - Spleen Splenic infarction - Extremities Limb pain Bone tenderness Rheumatism

Ischaemia viscosity & clumping Thrombosis Osteomyelitis Infarction of cells - Brain Cerebrovascular accident - Kidney Haematuria Low solubility Renal Failure of reduced HbS Sickling - Lung Pneumonia - Heart Heart failure Destruction Anaemia of sickle cells - Splenomegaly - Weakness - Lassitude - Abnormal skull radiographs

What you are expected to know by now

MENDELIAN GENETICS Basic Genetic Terminologies
Genotype, Phenotype Dominance, Recessive Genes, Alleles, Loci Homozygous, Heterozygous, Diploid, etc

Mendelian Laws
Law of Segregation Monohybrid Crosses, Punnett Square Law of Independent Assortment Dihybrid Crosses, Trihybrid Crosses, Partial Dominance, Backcross, Testcross

Sex Chromosome
Sex Determination Factorial calculations Sex Linkage Reciprocal Crosses Sex Linkage in Humans Influence of Barr Bodies Sex-influenced Traits, , Sex-Limited Traits

MODES OF INHERITANCE PEDIGREE ANALYSIS PENETRANCE AND EXPRESSIVITY PLEIOTROPY