sex-linked and mitochondrial inheritance (learning

Sex-linked and 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 X-

linked 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.

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

Figure 6.1Figure 6.1

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)

Sex determination in Mammals:the X-Y system

Karyotype designation: 46, XY (male)

46, XX (female) (homogametic)

Males are heterogameticGerm cells in testes (XY) produce sperms with

X: 50% Y: 50%

Females are homogameticGerm cells in ovaries (XX) produce only

X eggs

Figure 6.6

Sex Determination in Humans

Figure 6.6

X and Y ChromosomesX 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

Figure 6.3

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)

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

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 X-

linked.

X-linked Traits

Possible genotypesX+X+ −Homozyogus wild-type femaleX+Xm −Heterozygous female carrierXmXm −Homozygous mutant female

X+Y − Hemizygous wild-type maleXmY− 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_blindness/color_blindness.html

- Hemophilia = Disorder of blood-clotting http://www.ygyh.org

Figure 6.7Figure 6.7

Ichthyosis

X-linked Dominant Traits

Congenital generalized hypertrichosis

Figure 6.10

Sex-Limited TraitsTraits 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 TraitsTraits in which the phenotype expressed by a

heterozygote is influenced by sexAllele is dominant in one sex but recessive in the

otherThe gene may be autosomal or X-linked

Example:- Pattern baldness in humans (autosomal)

- A heterozygous male is bald, but a heterozygous female is not

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 6.12Figure 6.11

X InactivationA 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 testesc. male fertility

http://ghr.nlm.nih.gov/chromosome=Y

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

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 noncoding 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 “mini-chromosome”

Figure 5.8

Mitochondrion• Mitochondrial genes are transmitted from

mother to all of her offspring

Figure 5.7

Mitochondrial DisordersMitochondrial genes encode proteins that participate in

protein synthesis and energy production

Several diseases result from mutations in mtDNAaternallyinherited

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

Figure 5.9

• The mtDNA genome sequence may not the same in all mitochondria

• The phenotype reflects the proportion of mitochondria bearing the mutation