Genetics of Sex and Sex Linkage

Linkage is where multiple genes are associated with each other, altering inheritance patterns.
This lecture introduces the concept of linkage and the genetics of sex (biological sex, defined by chromosomes).

Biological sex is determined by chromosomes.
Aristotle's early ideas about sex determination involved the concept of 'heat' in men and 'chill' in women, influencing the sex of the child. Interestingly, temperature does affect sex determination in some reptiles like crocodiles.
Secondary sex characteristics (e.g., facial hair in men, sex organs, coloration in birds) define biological sex.
In nematodes, the presence of a single X chromosome determines maleness, while two X chromosomes result in a hermaphrodite.

In the early 1900s, scientists became interested in what determines biological sex.
Clarence McClung investigated chromosomes to understand heredity and sex determination.
Heinkein observed that male wasps were missing a physical presence that was present in the female.
Heinkein noticed that male wasps had either 11 or 12 chromosomes and he called the difference an "x element".
McClung worked with grasshoppers, finding 23 or 24 chromosomes in gametes, linking this "x element" to sex determination.

Allosomes: Sex chromosomes.
Autosomes: Non-sex chromosomes.
Humans have 23 pairs of chromosomes: 1 pair of allosomes and 22 pairs of autosomes.
Females are XX (homogametic, producing only X gametes).
Males are XY (heterogametic, producing X or Y gametes).
Males are considered hemizygous because the X and Y chromosomes are different.

The presence of the Y chromosome determines maleness in mammals.
XXY individuals (Klinefelter syndrome) have male characteristics due to the presence of the Y chromosome.
In fruit flies, the number of X chromosomes determines sex (one X is male, two or more are female).
In birds, ZW chromosomes determine femaleness (heterogametic), while ZZ is male (homogametic).

In 1959, a study of XX males revealed a 40 kilobase region coding for the SRY protein/gene on the X chromosome.
SRY gene (Sex-determining Region Y): Determines the sex pathway.
Embryos are sexually indifferent for the first 6-7 weeks.
The SRY gene activates around week 6 or 7, initiating testosterone production and male sexual development.
Without the SRY gene, the default pathway leads to estrogen production and female development.

The pseudoautosomal region (PAR) is a small region on the X and Y chromosomes with similar genes that allows the X and Y chromosomes to pair up during meiosis.

Wild-type flies have red eyes; mutants can have white eyes.
Homozygous red-eyed females ( $X^R X^R$ ) and hemizygous red-eyed males ( $X^R Y$ ).
White-eyed females ( $X^w X^w$ ) and white-eyed males ( $X^w Y$ ).
Sex-linked traits are genes located on a sex chromosome.
Notation: $X^R$ indicates the R gene is on the X chromosome.
Be careful to specify sex-linkage only when confirmed.

Crossing a white-eyed male ( $X^wY$ ) with a pure-breeding red-eyed female ( $X^R X^R$ ) results in all red-eyed offspring in the F1 generation.
Red eye color is dominant.

A reciprocal cross involves switching the phenotypes of the parents (red-eyed male with white-eyed female).
If results differ from the initial cross, the gene is sex-linked.
If the reciprocal cross gives the same result, it is not sex-linked.
The reciprocal cross helps determine if a gene is sex-linked by looking for differences in ratios and sex-specific expression.

Sex-linked traits are linked to individual sex chromosomes.
Most sex-linked traits are on the X chromosome because it is larger and has more genes.
Color blindness is an example of a sex-linked trait, more commonly expressed in males.
Males inherit X-linked traits from their mothers.
Y-linked traits (holandric traits) are passed from father to son.

Production of xanthine oxidoreductase for lactation in females (sex-limited).
Interferon regulatory factor 4 influences beard growth in males (sex-limited).
Pattern baldness: influenced by sex (sex-influenced).
Homozygous dominant (BB) leads to hair loss in both sexes, but the heterozygous condition (Bb) results in hair loss in males and not in females because levels of testosterone are related to this.