Download Sex-linked, Mitochondrial Inheritance (Learning Objectives

Sex-linked, Mitochondrial Inheritance (Learning Objectives)
• Explain how gender is determined in mammals.
• Define X- or Y-linked genes. How does the location of a gene on the
X chromosome affect its gender-related transmission?
• Use a Punnett square to determine the probability of passing of an Xlinked gene and the phenotype to girls or boys based on the
genotypes of the parents.
• Explain the difference between sex-limited traits and sex-influenced
traits.
• Explain X-inactivation and why it exists only in cells of females.
• Explain the functions of the Y chromosome gene and the pattern of
inheritance of Y-linked traits.
• Explain the pattern of inheritance of genes present on the
mitochondrial DNA why?
Sex determination in Mammals:
the X-Y system
Karyotype designation: 46, XY (male)
46, XX (female) (homogametic)
Males are heterogametic
Germ cells in testes (XY) produce sperms with
X: 50%
Y: 50%
Females are homogametic
Germ cells in ovaries (XX) produce only
X eggs
Sex Determination in Humans
Figure 6.6
Figure 6.6
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 repeated DNA segments
Figure 6.2
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 22 male-specific genes
including SRY and AZF (needed for
sperm production)
Figure 6.3
The inheritance of genes of X chromosome
• males have only a single X chromosome
• almost all the genes on the X have no
counterpart on the Y
• Genes are described as sex-linked or Xlinked.
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
X-linked Recessive Traits
Examples:
- Ichthyosis = Deficiency of an enzyme that removes
cholesterol from skin
- Color-blindness = Inability to see red and green
colors
http://www.biology.arizona.edu/human_bio/problem_sets/color_bli
ndness/color_blindness.html
- Hemophilia = Disorder of blood-clotting
http://www.ygyh.org
Ichthyosis
Figure 6.7
Figure 6.7
X-linked Dominant Traits
Congenital
generalized
hypertrichosis
Figure 6.10
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
X Inactivation
X inactivation occurs early in prenatal
development
It is an example of an epigenetic change
The XIST gene on the inactive X encodes an
RNA that binds to and inactivates the X
chromosome
Figure 6.11
Figure 6.12
X Inactivation
A female that expresses the phenotype
corresponding to an X-linked gene is a
manifesting heterozygote (calico cats)
Figure 6.12
Y-linked genes
The Y chromosome in males has 231 gene genes
whose protein products are involved in:
a. control of changing sex of the fetus from female to
male
b. development of male testes
c. male fertility
http://ghr.nlm.nih.gov/chromosome=Y
Gender
• Maleness or femaleness is determined at
conception
• Another level of sexual identity comes from the
control that hormones exert on development
• Finally, both psychological and sociological
components influence sexual feelings
19
During the fifth week of
prenatal development, all
embryos develop two sets of:
- Unspecialized (indifferent)
gonads
- Reproductive ducts:
Müllerian (female-specific) &
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)
Figure 6.1 Figure 6.1
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)
hormones are secreted and stimulate male
structures
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
22
Figure 6.4
Autosomal
Recessive
Autosomal
Recessive
Precocious puberty in males and females
XY females
(x-linked)
23
Homosexuality
• Person’s phenotype and genotype are
in-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
24
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
25
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
26
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
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
The gene may be autosomal or X-linked
Example:
- Pattern baldness in humans (autosomal)
- A heterozygous male is bald, but a
heterozygous female is not
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
Genetic Imprinting
• An inheritance process of gene expression
• Only one allele of imprinted genes is
expressed: mono-allelic expression (either
paternal or maternal allele)
• < 1% of the human genes are imprinted
• Found in mammals
Genetic Imprinting
• Dynamic process: erase and reestablished between generations
• Imprint is erased in germline cells and reestablished.
– In testes, parental imprint is reset
– In ovaries, maternal imprint is reset
• Passed on to next generation
Imprints are
erased during
meiosis
- Then
reinstituted
according to
the sex of the
individual
Figure 6.13
Mitochondrion
• Organelle providing cellular energy
• Contains small circular DNA called mtDNA
- 37 genes without non-coding sequences
• No crossing over and little DNA repair
• High exposure to free radicals
• Mutation rate is greater than nuclear DNA
• A cell typically
has thousands of
mitochondria,
and each has
numerous copies
of its “minichromosome”
Figure 5.8
Mitochondrion
• Mitochondrial genes are transmitted from
mother to all of her offspring
Figure 5.7
Mitochondrial Disorders
Mitochondrial genes encode proteins that participate in
protein synthesis and energy production
Several diseases result from mutations in mtDNA
maternally inherited
Examples:
- Mitochondrial myopathies – Weak and flaccid muscles
- Leber optical atrophy – Impaired vision
Ooplasmic transfer technique can enable woman to avoid
transmitting a mitochondrial disorder
Heteroplasmy
• The mtDNA genome sequence may not the
same in all mitochondria
• The phenotype reflects the proportion of
mitochondria bearing the mutation
Figure 5.9