Chapter 6
Matters of Sex
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
Learning Outcomes
• Describe the factors that contribute to whether
we are and feel male or female
• Distinguish between the X and Y chromosomes
• Discuss how manipulating sex ratio can affect
societies
• Distinguish between Y linkage and X linkage
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
2
Learning Outcomes
• Compare and contrast X-linked recessive
inheritance and X-linked dominant inheritance
• Discuss the inheritance pattern of a trait that
appears in only one sex
• Define sex-influenced trait
• Explain why X inactivation is necessary
• Explain how X inactivation is an epigenetic
change
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
3
Learning Outcomes
• Discuss how X inactivation affects the
phenotype in female mammals
• Explain the chemical basis of silencing the
genetic contribution from one parent
• Explain how differences in the timetables of
sperm and oocyte formation can lead to parentof-origin effects
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
4
Our Sexual Selves
• Maleness or femaleness is determined at
conception
• Another level of sexual identity comes from the
control that hormones exert on development of
reproductive structures
• Biological factors and social cues influence
sexual feelings
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
5
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 sex chromosome constitution and actions
of certain genes
• Specifically the SRY gene (sex-determining
region of the Y chromosome)
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
6
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)
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
7
Figure 6.2
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
8
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 replication
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
9
X and Y Chromosomes
Figure 6.1
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
10
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 6.3
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
11
SRY Gene
• Encodes a transcription factor protein
• Controls the expression of other genes
• Stimulates male development
• Sends signals to the indifferent gonads to destroy
female structures
• Stimulates development of male structures
• Testosterone and dihydrotesterone (DHT) are
secreted, stimulate male structures
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
12
Abnormalities in Sexual Development
• Androgen insensitivity syndrome = Lack of
androgen receptors
• Pseudohermaphroditism = Presence of male
and female structures at different stages of life
• 5-alpha reductase deficiency = Absence of DHT
• Congenital adrenal hyperplasia = High levels of
androgens
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
13
Figure 6.4
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
14
Homosexuality
• Person’s phenotype and genotype are consistent
• Physical attraction is toward members of the
same sex
• Homosexuality has been seen in all cultures for
thousands of years
• Documented in 500 animal species
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
15
Homosexuality
• Evidence suggests a complex input from both
genes and the environment
• Identical twins are more likely to be homosexual
than members of fraternal twin pairs
• Genetic markers were identified on the X
chromosome more often identical among pairs of
homosexual brothers
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
16
Egg with x chromosome
Fertilized by
Fertilized by
Sperm with X chromosome
Sperm with Y chromosome
Embryo with XY Chromosomes
Sex-determining region of the Y
chromosome (SRY) brings about
development of undifferentiated
gonads into testes
Chromosomal sex
Gonadal sex
Embryo with XX Chromosomes
No Y chromosome, so no SRY.
With no masculinizing influence,
undifferentiated gonads develop
into ovaries
Testes secrete masculinizing
hormones, including testosterone,
a potent androgen
In presence of testicular hormones,
undifferentiated reproductive tract
and external genitalia develop
along male lines
No androgens secreted
Phenotypic sex
With no masculinizing hormones,
undifferentiated reproductive
tract and external genitalia
develop along female lines
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
17
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
18
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
• Reflects medical conditions and environment
factors
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
19
Y-linked Traits
• Genes on the Y chromosome are said to be Ylinked
• Y-linked traits are very rare
• Transmitted from male to male
• A female does not have a Y chromosome
• Currently, identified Y-linked traits involve
infertility and are not transmitted
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
20
X-linked Traits
• Patterns of expression on the X chromosome
differ in females and males
• Females - X-linked traits are passed like
autosomal traits
• Males - A single copy of an X-linked allele
causes expression of the trait or illness
• Human male is considered hemizygous for Xlinked traits
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
21
Sex Determination in Humans
Figure 6.5
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
22
X-linked Recessive Inheritance
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
23
X-linked Recessive Traits
• Examples:
• Ichthyosis = enzyme deficiency blocks removal
of cholesterol from skin cells
• Color-blindness
• Hemophilia = Disorder of blood-clotting
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
24
Figure 6.6
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
25
Figure 6.7
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
26
X-linked Dominant Inheritance
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
27
X-linked Dominant Traits
Incontinentia
pigmenti
Figure 6.8
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
28
X-linked Dominant Traits
Congenital
generalized
hypertrichosis
Figure 6.9
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
29
Solving Genetic Problems
• Steps to follow:
• Look at the inheritance pattern
• Draw a pedigree
• List genotypes and phenotypes and their
probabilities
• Assign genotypes and phenotypes to parents
• Determine how alleles separate into gametes
• Unite the gametes in a Punnett square
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
30
Solving Genetic Problems
• Determine the phenotypic and genotypic
ratios for the F1 generation
• To predict further generations, use the
genotypes of the F1 and repeat steps 4 to 6
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
31
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
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
32
Sex-Influenced Traits
• Allele is dominant in one sex but recessive in
the other
• Difference in expression can be caused by
hormonal differences between sexes
• Example:
• Pattern baldness in humans
•
A heterozygous male is bald, but a heterozygous
female is not
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
33
X Inactivation
• Females have two alleles for X chromosome
genes but males have only one
• In mammals, X inactivation balances this
inequality in the expression of genes on the X
chromosome
• A female mammal is a mosaic for expression of
most genes on the X chromosome
• XIST gene encodes an RNA that binds to and
inactivates the X chromosome
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
34
X Inactivation
• X inactivation occurs early in prenatal
development
• The adult female has patches of tissue that differ in
their expression of X-linked genes
• Alters the phenotype and not the genotype
• It is an example of an epigenetic change
• An inherited change that does not alter the DNA
base sequence
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
35
Figure 6.10
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
36
X Inactivation
• Used to check the sex of an individual
• Nucleus of a cell of a female, during interphase,
contains a Barr body
• Consequence of X inactivation on the phenotype
• Homozygous X-linked genotypes - No effect
• Heterozygotes - Leads to expression of one allele
or the other
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
37
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 6.11
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
38
X Inactivation Animation
Please note that due to differing
operating systems, some animations
will not appear until the presentation is
viewed in Presentation Mode (Slide
Show view). You may see blank slides
in the “Normal” or “Slide Sorter” views.
All animations will appear after viewing
in Presentation Mode and playing each
animation. Most animations will require
the latest version of the Flash Player,
which is available at
http://get.adobe.com/flashplayer.
Figure 2.3
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
X Inactivation
• In humans, X inactivation can be used to identify
carriers of some X-linked disorders
• Lesch-Nyhan syndrome
• Affects the severity of Rett syndrome
• Unequal X inactivation pattern can occur if the
two X chromosomes have different alleles for a
gene that controls cell division
• Gives certain cells a survival advantage
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
40
Parent-of-Origin Effects
• Parental origin influences phenotype
• Age of onset
• Symptom severity
• Mechanisms of parent-of-origin effects
• Genomic imprinting
• Differences between developmental timetables of
sperm and oocytes
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
41
Genomic Imprinting
• Methyl (CH3) groups bind a gene or several
linked genes
• Prevent them from being accessed to synthesize
protein
• Parental effect on gene expression is seen as
diseases inherited from a parent
• Epigenetic alteration - Layer of meaning stamped
upon a gene without changing its DNA sequence
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
42
Methyl Groups
Figure 6.12
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
43
• Imprints are erased
during meiosis
• Then reinstituted
according to the
sex of the
individual
Figure 6.13
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
44
Importance of Genomic Imprinting
• Function of imprinting isn’t well understood,
may be a way to regulate abundance of key
proteins in the embryo
• Imprinted genes are in clusters along a
chromosome, controlled by imprinting centers
• One gene in a cluster could be essential for early
development
•
Others become imprinted due to bystander effect
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
45
Importance of Genomic Imprinting
• 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
• May be a concern in assisted reproductive
technologies
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
46
Teratoma
Figure 6.14
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
47
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
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
48
Imprinting and Human Disease
• Abnormal imprinting is associated with:
•
•
•
•
Diabetes mellitus
Autism
Alzheimer disease, schizophrenia
Male homosexuality
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
49
Imprinting and Human Disease
Deletion on chromosome 15 reveals imprinting
Figure 6.15
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
50
Different Timetables in Sperm and
Oocyte Formation
• Differences in development of sperm and
oocytes explain some parent-of-origin effects
• Huntington disease
• Noonan syndrome
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
51