Human GeneticsConcepts and Applications

Ninth Edition

RICKI LEWIS

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

PowerPoint® Lecture Outlines Prepared by Johnny El-Rady, University of South Florida

6 Matters of Sex

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SEX Determination

Maleness or femaleness is determined at conception

Humans are monoecious: meaning that each person can make one type of gamete either eggs or sperm

Dioecious organisms can make both types of gametes in the same body

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Sex Chromosomes Determine Gender

Human males are the heterogametic sex with different sex chromosomes, (XY)

Human females are the homogametic sex (XX)

In other species sex can be determined in many ways

- For example, in birds and snakes, males are homogametic (ZZ), while females are heterogametic (ZW)

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In grasshoppers, the female contains 24 chromosomes and is XX while the male contains 23 chromosomes and is XO

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X and Y Chromosomes

X chromosome

- Contains > 1,500 genes

- Larger than the Y chromosome

- Acts as a homolog to Y in males

Y chromosome

- Contains 231 genes

- Many DNA segments are palindromes and may destabilize DNA Figure 6.2

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Anatomy of the Y Chromosome

Figure 6.3

Pseudoautosomal regions (PAR1 and PAR2)

- 5% of the chromosome

- Contains genes shared with X chromosome

Male specific region (MSY)

- 95% of the chromosome

- Contains majority of genes including SRY and AZF (needed for sperm production)

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SRY Gene

Encodes a transcription factor protein

Controls the expression of other genes

Stimulates male development

Developing testes secrete anti-Mullerian hormone and destroy female structures

Testosterone and dihydrotesterone (DHT) are secreted and stimulate male structures

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Abnormalities in Sexual Development

Pseudohermaphroditism = Presence of male and female structures but at different stages of life

- Androgen insensitivity syndrome = Lack of androgen receptors

- 5-alpha reductase deficiency = Absence of DHT

- Congenital adrenal hyperplasia = High levels of androgens

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Abnormalities in Sexual Development

The degree to which pseudohermaphroditism disturbs the individual depends as much on society as it does on genetics.

In the Dominican Republic in the 1970s, 22 young girls reached the age of puberty and began to transform into boys.

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Abnormalities in Sexual Development

They had a form of 5-alpha reductase deficiency that was fairly common due to consanguinity ( relatives having children with relatives).

The parents were happy that they had had sons after all, and so these special adolescents were given their own gender nave at age 12.

11Figure 6.4

Figure 6.4

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Table 6.1

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Sex Ratios

The proportion of males to females in a human population

Calculated by # of males / # of females multiplied by 1,000

Primary sex ratio – At conception

Secondary sex ratio – At birth

Tertiary sex ratio – At maturity

Sex ratios can change markedly with age

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Sex Ratios

Sex ratios can be altered intentionally by a society

- Example: China’s one-child policy has led to a scarcity of females

Figure 6.5

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In China by the year 2020, 20 million men will find themselves without female partners as a result of the nations “ one-child” policy

The average number of births per woman fell from 5.4 in 1971 to 1.8 in 2001.

There is about 117 boys born for every 100 girls.The Chinese government is now promoting a “Care for Girls” program

which awards housing subsidies and scholarships to families with children

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At the other end of the human life cycle, sex ratio favors females in most populations.

For people over the age of 65 in the United States there is a ratio of 75 men for every 100 women

17Figure 6.6

Sex Determination in Humans

Figure 6.6

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Inheritance related to sex

Genes located exclusively on the x chromosome are called sex-linked

Genes that occur only on the Y chromosome can produce their effects only in males and are called Holandric genes

The mechanisms where a given trait is limited to one sex is called sex-limited and fi dominance of a given allele depends on the sex of the bearer is called sex-influenced.

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Y-linked Traits

Genes on the Y chromosome are said to be Y-linked

Y-linked traits are very rare

Transmitted from male to male

No affected females

Currently, identified Y-linked traits involve infertility and are not transmitted

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X-linked Traits ( we will do some examples on the board

Possible genotypes

X+X+ Homozyogus wild-type female

X+Xm Heterozygous female carrier

XmXm Homozygous mutant female

X+Y Hemizygous wild-type male

XmY Hemizygous mutant male

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X-linked Recessive Inheritance

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X-linked Recessive Traits

Examples:

- Ichthyosis = Deficiency of an enzyme that removes cholesterol from skin

- Color-blindness = Inability to see red and green colors ( only about 0.4 % are girls)

- Hemophilia = Disorder of blood-clotting

23Figure 6.7

Figure 6.7

24Figure 6.8

Figure 6.8

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X-linked Dominant Inheritance

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X-linked Dominant Traits

Incontinentia pigmenti

A newborn girl with IP has yellow, pus filled vesicles on her limbs, the lesions become warty and eventually give way to brown splotches that remain for life

Figure 6.9

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X-linked Dominant Traits

Congenital generalized hypertrichosis

Produces many extra hair follicles, and more denser more abundant upper body hair. An affected man would pass the trait to all his daughter, but non of his sons. Why?Figure 6.10

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Solving Genetic Problems

Steps to follow:

1) Look at the inheritance pattern

2) Draw a pedigree

3) List genotypes and phenotypes and their probabilities

4) Assign genotypes and phenotypes

5) Determine how alleles separate into gametes

6) Use Punnett square to determine ratios

7) Repeat for next generation

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Sex-Limited Traits

Traits that affect a structure or function occurring only in one sex

The gene may be autosomal or X-linked

Examples:

- Beard growth

- Milk production

- Preeclampsia in pregnancy

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Sex-limited characteristics do some examples on board

Genotype male chickens female HH Hen feathered Hen feathered

Hh Hen feathered Hen feathered

hh cock-feathered Hen feathered

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Sex-Influenced Traits

Traits in which the phenotype expressed by a heterozygote is influenced by sex

Allele is dominant in one sex but recessive in the other

Example:

- Pattern baldness in humans

- A heterozygous male is bald, but a heterozygous female is not

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Sex influenced traits

Baldness: do some problems on the board

Genotype Men women

BB bald Bald

Bb bald not

bb not not

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X Inactivation

Females have two alleles for X chromosome genes but males have only one

In mammals, X inactivation balances this inequality and one X chromosome is randomly inactivated in each cell

The inactivated X chromosome is called a Barr body

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X Inactivation

X inactivation occurs early in prenatal development

It is an example of an epigenetic change

- An inherited change that does not alter the DNA base sequence

The XIST gene encodes an RNA that binds to and inactivates the X chromosome

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Barr Bodies

Were discovered in 1940s in female cats but not male

Barr body is the inactive X chromosome in a female somatic cell,

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37Figure 6.12Figure 6.11

38Figure 2.3

X Inactivation Animation

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X Inactivation

A female that expresses the phenotype corresponding to an X-linked gene is a manifesting heterozygote

X inactivation is obvious in calico cats

LOOK AT KEY ON HOW TO SOLVE THESE PROBLEMS

Figure 6.12

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X inactivation

Theoretically, X inactivation evens out the sexes for expression of X-linked genes.

In actuality, a female may not be equivalent, in gene expression, to a male because she has two cell populations, where the male has only one

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X inactivation

A situation in which being heterozygote for an X-linked gene is harmful is craniofrontonasal syndrome. Males and homzygous females have asymmetrical facial features

Heterozygous females have much more sever phenotypes with very abnormal faces resulting from abnormal fusing of skull bones

42

Rett Syndrome: Curious inheritance pattern

Nearly always affects femalesOne symptom is that the girls do strange things with their hands__ uncontrollably taping objects, clapping , repeatedly put hands to mouth and wring their handsThis is dominant and in 99% of cases is not passed from parent to child but arises anew

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Genomic Imprinting

The phenotype of an individual differs depending on the gene’s parental origin

Genes are imprinted by an epigenetic event: DNA methylation

- Methyl (CH3) groups bind to DNA and suppress gene expression in a pattern determined by the individual’s sex

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Imprints are erased during meiosis

- Then reinstituted according to the sex of the individual

Figure 6.13

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Importance of Genomic Imprinting

Function of imprinting isn’t well understood, but it may play a role in development

Research suggests that it takes two opposite sex parents to produce a healthy embryo

- Male genome controls placenta development

- Female genome controls embryo development

Genomic imprinting may also explain incomplete penetrance

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Imprinting and Human Disease

Two distinct syndromes result from a small deletion in chromosome 15

- Prader-Willi syndrome

- Deletion inherited from father

- Angelman syndrome

- Deletion inherited from mother

The two syndromes may also result from uniparental disomy

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Deletion on chromosome 15 reveals imprinting

Imprinting and Human Disease

Figure 6.16

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Turner Syndrome

Called the XO syndrome

1 in 2,500 female births

99% of affected fetuses die in utero

Features include short stature, webbing at back of neck, incomplete sexual development (infertile), impaired hearing

Individuals who are mosaics may have children

No bar bodies in cells

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XYY Syndrome

Also known as Jacobs syndrome

1 in 1,000 male births

96% are phenotypically normal

Modest phenotypes may include great height, acne, speech and reading disabilities

Studies suggesting increase in aggressive behaviors are not supported

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Triplo-X

Called the XXX syndrome

1 in 1,000 female births

Few modest effects on phenotype include tallness, menstrual irregularities, and slight impact on intelligence

X-inactivation of two X chromosomes occurs and cells have two Barr bodies

May compensate for presence of extra X

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Klinefelter Syndrome

Called the XXY syndrome

1 in 500 male births

Phenotypes include:

- Incomplete sexual development

- Rudimentary testes and prostate

- Long limbs, large hands and feet

- Some breast tissue development

Most common cause of male infertility

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XXYY Syndrome

Likely arises due to unusual oocyte and sperm

Associated with more severe behavioral problems than Klinefelter syndrome

- AAD, obsessive compulsive disorder, learning disabilities

Individuals are infertile

Treated with testosterone

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XYY Syndrome

Also known as Jacobs syndrome

1 in 1,000 male births

96% are phenotypically normal

Modest phenotypes may include great height, acne, speech and reading disabilities

Studies suggesting increase in aggressive behaviors are not supported