Transcript Human Genetics

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
- Many DNA segments are
palindromes and may
destabilize DNA
Figure 6.1
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Anatomy of the Y Chromosome
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)
Figure 6.2
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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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Figure 6.3
Figure 6.4
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Homosexuality
Homosexuality has been seen in all
cultures for thousands of years
Documented in 500 animal species
Evidence suggests a complex input from
both genes and the environment
Research in this area is controversial
Studies of identical and fraternal twins
Identifying possible markers
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Table 6.1
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Sex Determination in Humans
Figure 6.4
Figure 6.6
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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
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Figure 6.5
Figure 6.7
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Figure 6.6
Figure 6.8
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X-linked Dominant Inheritance
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X-linked Dominant Traits
Incontinentia
pigmenti
Figure 6.7
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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
The gene may be autosomal or X-linked
Examples:
- Beard growth
- Milk production
- Preeclampsia in pregnancy
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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
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Figure 6.9
Figure 6.12
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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
The two syndromes may also result from
uniparental disomy
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