STEMLA - Sex Determination & Sex-Linked Inheritance

Genetic Maternal Effect

  • Offspring phenotype controlled by mother’s genotype, not their own.

  • Mechanism: maternal gene product deposited in egg cytoplasm (e.g., direction of snail shell coiling).

Extensions of Mendelian Principles

  • Mendel’s laws remain valid but cannot explain all inheritance patterns.

  • Added concepts: genetic maternal effect, sex-linked inheritance, dosage compensation, etc.

Sexual Reproduction Basics

  • Two processes alternate: meiosis ➔ haploid gametes; fertilization ➔ diploid zygote.

  • Sex = sexual phenotype; defined by gamete size: sperm (small) vs. egg (large).

Chromosomal Sex-Determining Systems

  • XX-XO: females XX (homogametic), males XO (heterogametic).

  • XX-XY: females XX, males XY; male heterogametic ➔ 1{:}1 sex ratio.

  • ZZ-ZW: males ZZ (homogametic), females ZW (heterogametic).

  • Pseudoautosomal regions: homologous segments on X & Y for pairing in meiosis.

Genic Sex Determination

  • No cytologically distinct sex chromosomes; sex decided by alleles at one or more loci.

Environmental Sex Determination

  • Temperature or other environmental cues influence sex (e.g., reptiles: warm ➔ females in turtles).

Sex Determination in Drosophila

  • Primary signal: X-linked genes balance, summarized as \text{X:A} ratio:

    • \text{X:A}=1.0 ➔ female

    • \text{X:A}=0.5 ➔ male

    • 0.5<\text{X:A}<1.0 ➔ intersex

    • >1.0 ➔ metafemale, <0.5 ➔ metamale.

  • Autosomes affect timing, indirectly modulating X-gene activity.

Sex Determination in Humans

  • Presence of Y (specifically SRY) ➔ testes ➔ testosterone & Müllerian-inhibiting substance ➔ male pathway.

  • Without SRY ➔ ovaries ➔ female pathway.

Aneuploidy Phenotypes

  • Turner XO: female, short, sterile.

  • Klinefelter XXY/XXXY/XXYY: male, tall, small testes, reduced hair.

  • Poly-X XXX/XXXX/XXXXX: female, tall; ↑X ➔ intellectual disability severity ↑.

  • XYY males: tall, usually normal fertility & IQ.

SRY Gene

  • Located on Y short arm; presence alone converts XX embryos to anatomical males (sterile).

Sex-Linked Characteristics

  • X-linked: genes on X; males hemizygous.

  • Y-linked (holandric): genes on Y; transmitted father ➔ all sons only.

X-Linked Inheritance Patterns

  • Reciprocal crosses differ.

  • Male inherits X only from mother; trait never passes father ➔ son directly.

  • Example notation: X^{w}Y (white-eyed male), X^{w}X^{w} (white-eyed female).

Dosage Compensation (Placental Mammals)

  • Goal: equalize X-linked expression across sexes.

  • Females: global up-regulation of both X + random inactivation of one X (Lyon hypothesis).

  • Result: functional hemizygosity; females are mosaics for X-linked gene expression.

Barr Bodies

  • Inactivated X appears as Barr body in nucleus.

  • Count formula: \text{Barr bodies}=n_X-1.

  • Examples: XX \rightarrow 1, XO \rightarrow 0, XXY \rightarrow 1, XXXX \rightarrow 3.

Y-Linked Traits & Markers

  • Present only in males, transmitted solely through paternal line.

  • Y-DNA markers (unique SNP combinations) trace male ancestry & migration (e.g., Thomas Jefferson lineage study).

Recognizing Sex-Linked Inheritance

  • Y-linked: males only, father ➔ all sons, never through female line.

  • X-linked: different reciprocal cross outcomes; father never passes trait to sons; daughters may be carriers.

  • Distinguish from sex-influenced (autosomal, hormone-dependent) or sex-limited traits.