Transcript X chromosome

Human Genetics
Concepts and Applications
Tenth Edition
RICKI LEWIS
6
Biol 4355 - Genética
Humana
Capítulo 6 –
Sobre
el
Matters of Sex
Sexo
UPR – Aguadilla
JA Cardé, PhDPowerPoint
Lecture Outlines
Prepared by Johnny El-Rady, University of South Florida
®
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Objectives
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To describe the factors that contribute to
maleness of femaleness
To distinguish between Y and X linkage
To discuss the inheritance pattern of a trait that
appears in only one sex
To explain X inactivation: epigenetic and effects
on phenotype
To explain the chemical basis of silencing the
genetic contribution of a parent
To review examples of imprinting
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Our Sexual Selves
Maleness or femaleness is determined at
conception (which chromosome?)
Another level of sexual identity comes from
the control that hormones exert on
development
Finally, both psychological and sociological
components influence sexual feelings
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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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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) (Wnt4, others)
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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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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)
Gen o genes para masculinidad?
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
46XX males vs 46 XY females = SRY
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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
- XY but female phenotype
- 5-alpha reductase deficiency = Absence of DHT
- males with SRY+ and testes but female
pheno
- 12 y/o transformation
- Congenital adrenal hyperplasia = High levels of
androgens
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- PSD males (3y/o), male 2ndry charac in fem
Figure 6.3
Androgen
insensivity
syndrome
Figure 6.4
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Homosexuality
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Seen in all cultures for thousands of years
documented in 500 animal species
Evidence suggests a complex input from
both genes and the environment
Phenotype and genotype consistent
Atraction towards the same sex
Studies of identical and fraternal twins
Identifying possible markers in X, presents
among pair of homosexuals more often
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Sexual Identity Components
Table 6.1
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Sex Ratios
Mendel: predicts that equals number of male and
females
- social, environment can select for one gender
The proportion of males to females in a human
population should be 1:1
Calculated by # of males / # of females multiplied by 1,000
Primary sex ratio – At conception (EU, 1050)
Secondary sex ratio – At birth (China, India)
Tertiary sex ratio – At maturity, (EU 65+ , 720)
Sex ratios can change markedly with age
- medical conditions or environment affects sexes
differentially
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Y-linked Traits
Genes on the Y chromosome
Y-linked traits are very rare
Transmitted from male to male
No affected females
Currently, identified Y-linked traits involve infertility and BTW,
obviously not transmitted
X – has more genes than Y, more mutants with
consequences
Account for ~10% of Mendelian diseases (one gene)
Genes in X have different pattern of expression in each sex
In females are passed as autosomal (two copies)
In males are passed as dominant (one copy)
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Sex Determination in Humans
Figure 6.4
Figure 6.6
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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 B = Disorder of blood-clotting
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Ichthyosis = Deficiency of an
enzyme that removes cholesterol
from skin
Middle-aged man
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1 y/o grand-son skin resembles
his.
Cholesterol removed by an
enzyme, blocked in this condition
Daughter produced half the
enzyme ammount
Figure 6.7
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Figure 6.5
Figure 6.6
Figure 6.8
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X-linked Dominant Inheritance
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X-linked Dominant Traits
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Rare traits
Expression differ between
sexes (severity)
Females : swirls of skin,
melanin, puz filled vesicles,
warts, spots)
Males : die before born
Carriers have 25% of
misscarriages
Incontinentia pigmenti
Figure 6.7
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X-linked Dominant Traits
Congenital generalized
hypertrichosis
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Many extra follicules
More dense and
abundant hair upper body
Females patchy and
milder (hormones and
another X)
Note: no sons inherited
the condition
Figure 6.8
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Solving Problems: X linked
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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Kallman Syndrome - Assigned
Causes very poor or absent sense of smell and small
gonads.
1) Its X linked, recessive
2) Tanisha does not have it, but her brother Jamal an her
maternal cousin Malcolm (her mother’s sisters’ child) have it
3) Tanisha’s and Malcolm’s parents are unaffected
4) Tanisha’s husband Sams is unaffected
5) Tanisha and Sam want to know the risk that a son would
inherit the condition. Sam has no afffected relatives.
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Sex-Limited Traits
Traits that affect a structure or function of a body
part occurring only in one sex
The gene may be autosomal or X-linked
Examples:
- Beard growth – women do not grow it, but can pass the
mutation to sons
- Milk production – males not make milk but can pass the
trait
- Preeclampsia in pregnancy – male genes affect
placenta, that’s affect women bp (Assigned)
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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
- trait may be affected by hormonal differences
- Gene for baldness have to alleles (Hairy (h) and bald (H)
- Males: H dominant over h, females inverse
- males Hh=?; females Hh = ? Females HH ?
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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, the women becomes a mosaic for
expression of most genes on the X
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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
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A female that expresses the phenotype corresponding to
an X-linked gene is a manifesting heterozygote
In homozygous X linked genotypes, has no effect
X inactivation is obvious in calico
cats (XB/XY)
Incontinentia pigmenti
Hunter syndrome/ Fabry dis
Lesch-Nyhan Syndrome (Asig)
Figure 6.10
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An allele of and X gene that
stimulate cell division?
Two X gene proteins interacts
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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
Imprinting pattern is passed from cell to cell in
mitosis but not from individual to individual in
meiosis
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Imprints are erased during
meiosis
- Then reinstituted
according to the sex of
the individual
During mitosis replication
pattern is passed exactly or
imprinted
During meiosis the CH3 pattern
is removend and reset,
according to cygote sex.
Womens can have son and
Figure 6.11
males can have daughter
without passing their specific
parental imprints
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Importance of Genomic Imprinting
Function of imprinting isn’t well understood, but it
may play a role in development – brains genes
Research suggests that it takes two opposite sex parents to
produce a healthy embryo
- Male genome controls placenta- (ovum with 2 male
pronuclei) development but tiny and stopped
- Female genome controls embryo development - (ovum
with 2 females pronuclei) – developed but aberrant
placenta
Genomic imprinting may also explain incomplete penetrance
(one imprinted gene can silence de dominant mutant
alllele.
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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; genes not normally
imprinted, are missing, only mothers expressed
- Eating disorder – obesity, compulsive
- Angelman syndrome - Deletion inherited from mother
-autism, lack of muscle coordination
The two syndromes may also result from uniparental
disomy
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Imprinting and Human Disease
Deletion on chromosome 15 reveals imprinting
Figure 6.14
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