Study Notes for BIO 110 Human Genetics: Sex Chromosomes & X Inactivation

BIO 110 Human Genetics: Sex Chromosomes & X Inactivation

Today’s Schedule

  • Topics Covered:

    • Male / Female Development & Determination

    • X & Y Linked Traits

    • X Inactivation

    • Genomic Imprinting

MALE/FEMALE DEVELOPMENT & DETERMINATION

Sex Identity

  • Determined at conception by:

    • X & Y chromosomes

    • Hormonal influences

    • Biological factors and social cues

Sex Chromosomes Determine Gender

  • Human males are heterogametic: XY

  • Human females are homogametic: XX

  • In other species, sex determination varies:

    • Example: In birds and snakes, males are homogametic (ZZ), while females are heterogametic (ZW)

Sex Determination in Humans

  • Sperm contributes X or Y chromosome:

    • Male: X Y

    • Female: X X

  • Eggs always contribute X chromosome.

Indifferent Stage of Gonad Development

  • Indifferent Stage: Gonads have not yet developed into testes (male) or ovaries (female).

    • SRY gene: Determines developmental pathway:

    • Absent: Müllerian duct forms female structures (Ovaries, Uterus, etc.)

    • Present: Wolffian duct forms male structures (Testes, Prostate, etc.)

  • Structures:

    • Male: Ductus deferens, Penis

    • Female: Uterine tube, Vagina

X and Y Chromosomes

Anatomy of the Y Chromosome

  • Pseudoautosomal regions (PAR1 and PAR2):

    • 5% of the Y chromosome

    • Contains genes shared with the X chromosome

  • Male specific region (MSY):

    • 95% of the Y chromosome

    • Contains genes like SRY and AZF necessary for sperm production

SRY Gene

  • Function:

    • Encodes a transcription factor protein

    • Controls the expression of other genes involved in male development

    • Signals indifferent gonads to destroy female structures

    • Stimulates development of male structures

  • Hormonal Contributions:

    • Testosterone and dihydrotestosterone (DHT) stimulate male structure development

Abnormalities in Sexual Development

  • Androgen insensitivity syndrome: Lack of androgen receptors

  • Pseudohermaphroditism: Presence of both male and female structures at different life stages

    • 5-alpha reductase deficiency: Absence of DHT, affecting male characteristics

    • Congenital adrenal hyperplasia: High levels of androgens leading to ambiguous genitalia

Mutations Affecting Male Sexual Development

  • Various interventions at gene points:

    • SRY: Triggers testis formation (congenital adrenal hyperplasia)

    • Androgen receptors: Required for the development of typical male structures (androgen insensitivity syndrome)

    • Testosterone: Promotes internal male structures including Epididymides and Ejaculatory ducts

    • Dihydrotestosterone: Required for external male structures like the prostate and penis

Homosexuality

  • Definition:

    • A person's phenotype and genotype align, characterized by attraction to the same sex

  • Evidence suggests both genetic and environmental factors contribute:

    • Higher likelihood in identical twins

    • Specific genetic markers identified on the X chromosome among homosexual brothers

X & Y LINKED TRAITS

Y-linked Traits

  • Definition:

    • Genes located on the Y chromosome

  • Characteristics:

    • Very rare

    • Transmitted from male to male

X-linked Traits

  • Expression patterns differ between sexes:

    • In females: X-linked traits behave like autosomal traits

    • In males: A single copy of an X-linked allele leads to expression of the trait or condition

  • Human males termed hemizygous for X-linked traits

Examples of X-linked Traits

  • Ichthyosis: An X-linked recessive trait

  • Hemophilia: Genetic pattern:

    • Genotypes involved in inheritance

    • Family pedigree illustrating passage of the hemophilia allele

X-linked Dominant Inheritance

  • Criteria:

    1. Expressed in females with one copy

    2. More severe in males

    3. High miscarriage rates due to male lethality

    4. Passed from male to all daughters, but no sons

Examples of X-linked Dominant Traits

  • Incontinentia pigmenti: Presentation and inheritance patterns

  • Hypertrichosis: Expression in males versus females

Sex-Limited Traits

  • Definition:

    • Traits affecting structures/functions occurring only in one sex

    • Genes may be autosomal or X-linked

Sex-Influenced Traits

  • Example: Pattern baldness in males

X INACTIVATION

X Inactivation in Females

  • Mechanism:

    • Females possess two alleles for X-linked genes; males have only one

    • XIST gene: Encodes RNA that binds and inactivates one X chromosome, leading to the formation of a Barr body

X Inactivation: Calico Cats

  • Concept of manifesting heterozygote: A female that expresses different X-linked gene phenotypes due to X inactivation, illustrated by the distinct coloring patterns in calico cats

GENOMIC IMPRINTING

Definition of Genomic Imprinting

  • Epigenetic alteration where methyl (CH3) groups bind to genes, preventing protein synthesis

Mechanism of Imprinting

  • Imprints erased during meiosis and reinstated according to the sex of the individual

Imprinting and Human Disease

  • Example on chromosome 15:

    • Consequences of paternal deletion vs. maternal deletion:

    • Prader-Willi syndrome: Results from paternal deletion

    • Angelman syndrome: Results from maternal deletion

Parent-of-Origin Effects in Conditions

  • Some conditions exhibit different expressions based on whether inherited from mother or father, notable examples include:

    • Huntington disease

    • Noonan syndrome