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Human Genetics Concepts and Applications

Tenth 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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Our Sexual Selves Maleness or femaleness is determined at

conception

Another level of sexual identity comes from the control that hormones exert on development

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Sexual Development During the fifth week of prenatal development, all

embryos develop two sets of: - Unspecialized (indifferent) gonads - Reproductive ducts – Müllerian (female-specific) and Wolffian (male-specific)

An embryo develops as a male or female based on

the absence or presence of the Y chromosome - Specifically the SRY gene (sex-determining region of the Y chromosome)

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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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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

Figure 6.1

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Anatomy of the Y Chromosome

Figure 6.2

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 dihydrotestosterone

(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 - 5-alpha reductase deficiency - Congenital adrenal hyperplasia = High levels of androgens

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Androgen insensitivity syndrome

•  Androgen insensitivity syndrome = Lack of androgen receptors

•  Androgens are male hormones, testosterone and dihydrotestosterone

•  Person is XY, but cells don’t receive the signal to develop as male, so the person looks female.

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5-alpha reductase deficiency

•  5-alpha reductase deficiency = Absence of DHT •  XY individual with normal Y chrmosome. •  Male reproductive tract develops normally on the

inside. •  5-alpha reductase catalyzes the reaction of

testosterone to form DHT.Without DHT, a penis cannot form.

•  At puberty, when the adrenal glands start to produce testosterone, this XY person who though she was female will begin developing male secondary sex characteristics, including a penis.

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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 Determination in Humans

Figure 6.4

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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

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

- Hemophilia = Disorder of blood-clotting - Duchenne Muscular Dystrophy = muscles deteriorate over time

18 Figure 6.7!

Figure 6.5

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Duchenne Muscular Dystrophy

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Duchenne muscular dystrophy.

•  Caused by a mutation in the gene that codes for dystrophin, which is located on the X chromosome.

•  Muscles deteriorate over time. •  A child with DMD is often wheelchair-bound

by the age of 12. •  Survival is increasing into the 20s and 30s.

Previously, these young men died in their teens.

22 Figure 6.8!

Figure 6.6

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X-linked Dominant Inheritance

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X-linked Dominant Traits

Congenital generalized hypertrichosis

Figure 6.8

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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 but can be passed on by either sex.

The gene may be autosomal or X-linked

Examples: - Beard growth - Milk production - Preeclampsia in pregnancy

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Sex Limited traits

•  Beard growth—only men grow beards, but women can pass on a gene for heavy beard growth to their sons.

•  Men can also pass on genes that affect milk production in daughters even though they themselves don’t produce milk.

•  Preeclampsia—sudden spike in blood pressure late in pregnancy.

•  Placental development can be affected by father’s genes.

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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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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

31 Figure 6.12!Figure 6.9

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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 Figure 6.10

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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 6.11

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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

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Deletion on chromosome 15 reveals imprinting!

Imprinting and Human Disease

Figure 6.14

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Prader-Willi and Angelman syndromes

•  Angelman affects the nervous system causing seizures, motor problems, intellectual disabilities and difficulties with speech.

•  Prader-Willi is characterized by poor muscle tone, chronic hunger, incomplete sexual development, and short stature.