6.2.5 - Sex Linkage

• In humans, sex is determined by one of the 23 pairs of chromosomes, called the sex chromosomes.
• The other 22 pairs of chromosomes are called autosomes. Autosomes are homologous - contain the same genes on the same loci and are the same length, but may have different alleles of that gene.
• In mammals:

  XX - Female (homogametic)

  XY - Male (heterogametic)
• Sex chromosomes are partly homologous because the Y is very small (about 55 genes), compared the the X (about 900 genes). A small part of one matches a small part of the other, so that these chromosomes can pair up before meiosis.
• The human X chromosome contains over 1000 genes that are involved in determining many characteristics or metabolic functions, not concerned with sex determination, and most of these have no partner alleles on the Y chromosome.
• If a female has one abnormal allele on one of her X chromosomes, she will probably have a functioning allele of the same gene on her other X chromosome.
• If a male inherits, from his mother, an X chromosome with an abnormal allele for a particular gene, he will suffer from a genetic disease, as he will not have a functioning allele for that gene.
• Males are functionally haploid or hemizygous for many X-linked genes. If they inherit an abnormal gene on the X chromosome, they have no functional allele on the Y.
• Genetic sex-linked diseases are thus more common in men, such as Haemophilia A and colour-blindness.
• A person with haemophilia A is unable to clot blood fast enough. Injuries may cause bleeding or an internal haemorrhage.
• One of the genes on the non-homologous region of the X chromosome codes for a blood-clotting protein called Factor 8. A mutated form of the allele codes for non-functioning Factor 8.
• A female with one abnormal allele and one functioning allele produces enough factor 8 to enable blood to cot normally when required, but the female is a carrier for the disease. If a female passes the X chromosome with the faulty allele to her son, he will have no functioning allele for Factor 8 on his Y chromosome. This means he will suffer from Haemophilia A.
• One of the genes involved in coding for a protein involved in colour vision is on the X chromosome, but not on the Y chromosome. A mutated allele of this gene may result in colour blindness, an inability to distinguish between red and green. A female with one abnormal allele and one functioning allele will not suffer from colour blindness, but a male with an abnormal allele on his X chromosome will not have a functioning allele on his Y chromosome and will therefore suffer from red-green colour blindness.
• One of the genes, C, for coat colour in cats is sex linked. It is only on the non-homologous region of the X chromosome:

  • Co produces ginger fur.
  • Cb produces black fur.
• These alleles are codominant - cats with genotype Xco and Xcb are tortoiseshell with patches of both black and ginger fur.
• Both the orange and black alleles contribute to the phenotype, but the orange allele is only expressed in cells where the X chromosome bearing the black allele is inactivated, and vice versa.
• Male cats may either be black or ginger but not tortoiseshell; they have only 1 X chromosome.
• It may appear that females have twice the number of X-linked genes being expressed as do males, however a mechanism prevents this disparity. In every female cell nucleus, one X chromosome is inactivated. Determination of which member of the pair of X chromosomes becomes inactivated is random and happens during early embryonic development.