Sex linkage is the phenotypic expression of an allele related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of inheritance. Since humans have many more genes on the X than the Y, there are many more X-linked traits than Y-linked traits.
In mammals, the female is the homozygous sex, with two X chromosomes (XX), while the male is heterozygous, with one X and one Y chromosome (XY). Genes on the X or Y chromosome are called sex linked genes.
In birds, the opposite is true: the male is the homozygous sex, having two Z chromosomes (ZZ), and the female (hen) is heterozygous, having one Z and one W chromosome (ZW).
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X-linked recessive traits are expressed in all heterogametics, but are only expressed in those homogametics that are homozygous for the recessive allele. For example, an X-linked recessive allele in humans causes hemophilia. Hemophilia is much more common in males than females because males are hemizygous - they only have one copy of the gene in question - and therefore express the trait when they inherit one mutant allele. In contrast, a female must inherit two mutant alleles, a less frequent event since the mutant allele is rare in the population. Tsarevich Alexei of Russia was the most famous sufferer of X-linked hemophilia, and his disease may have played an important role in the overthrow of the imperial regime, which changed the course of history for millions of people.
The incidence of recessive X-linked phenotypes in females is the square of that in males (squaring a proportion less than one gives an outcome closer to 0 than the original). If 1 in 20 males in a human population are green colour blind, then 1 in 400 females in the population are expected to be colour blind (1/20)*(1/20).
X-linked traits are maternally inherited from carrier mothers or from an affected father. Each son born to a carrier mother has a 50% probability of inheriting the X-chromosome carrying the mutant allele. There are a few Y-linked traits; these are inherited from the father.
In classical genetics, a reciprocal cross is performed to test if a trait is sex-linked.
| (A) | (B) | (C) |
| Illustration of some X-linked heredity outcomes (A) the affected father has one X-linked dominant allele, the mother is homozygous for the recessive allele: only daughters (all) will be affected. (B) the affected mother is hemizygous with one copy of the X-linked dominant allele: both daughters and sons will have 50% probability to be affected. (C) the hemizygous mother is called "carrier" because she has one copy of the recessive allele: sons will have 50% probability to be affected, 50% of unaffected daughters will become carriers like their mother [2]. |
Autosomal Dominant Inheritance
Characteristics of Autosomal Dominant Inheritance: • The child of an affected parent has a 50% chance of inheriting the parent's mutated allele and thus being affected with the disorder. • A mutation can be transmitted by either the mother or the father. All children, regardless of gender, have an equal chance of inheriting the mutation
Examples: • Tuberous sclerosis • Marfan syndrome • Neurofibromatosis • Huntington's disease • Retinoblastoma • Waardenburg syndrome • Myotonic dystrophy • Familial hypercholestrolemia (LDL receptor defect Type IIa) • Adult polycystic kidney disease • von Hippel Lindau • Familial adenomatous polyposis and Peutz Jeghers Syndrome • Hereditory spherocytosis • Achondroplasia • Ehlor's Danlos (vascular type) • Acute intermittent porphyria • Hypertrophic Obstructive Cardiomyopathy (HOCM) • Von Willebrand Disease • Polydactyly • Osteogenesis Imperfecta (Except Type VII) • Hereditary hemorrhagic telengiactasia (Osler-weber-rendu syndrome) • Osteopetrosis Type II (Adult type) • Hypokalemic Periodic Paralysis
Autosomal Recessive Inheritance
Characteristics of Autosomal Recessive Inheritance: • An individual will be a "carrier" if they possess one mutated allele and one normal gene copy. • There is a 50% chance that a carrier will transmit a mutated gene to a child. • If two carrier parents have a child there is a: o 25% chance that both will transmit the mutated gene; in this case, the child will inherit only mutated copies of the gene from both the mother and the father and thus will be affected with the disorder. o 50% chance that one carrier parent will transmit the mutated gene and the other will transmit the normal gene; in this case, the child will have one mutated gene and one normal gene and will be a carrier of the disorder. o 25% chance that both carrier parents will transmit the normal gene; in this case the child will have only normal genes and will not be affected and will not be a carrier.
Examples:
• cystic fibrosis, • sickle-cell disease, • Tay-Sachs disease, • Niemann-Pick disease, • spinal muscular atrophy, • Roberts’s syndrome.
X-Linked Dominant Inheritance
Characteristics of X-Linked Dominant Inheritance: • A male or female child of an affected mother has a 50% chance of inheriting the mutation and thus being affected with the disorder. • All female children of an affected father will be affected (daughters possess their fathers' X-chromosome). • No male children of an affected father will be affected (sons do not inherit their fathers' X-chromosome).
Examples:
• Alport's syndrome • Aarsog's syndrome • Coffin - Lowry syndrome (CLS) • idiopathic hypoparathyroidism • incontinentia pigmenti • ornithine carbamoyl transferase deficiency • Rett syndrome (RS) • vitamin D resistant rickets • fragile X syndrome
X-Linked Recessive Inheritance
Characteristics of X-Linked Recessive Inheritance: • Females possessing one X-linked recessive mutation are considered carriers and will generally not manifest clinical symptoms of the disorder. • All males possessing an X-linked recessive mutation will be affected (males have a single X-chromosome and therefore have only one copy of X-linked genes). • All offspring of a carrier female have a 50% chance of inheriting the mutation. • All female children of an affected father will be carriers (daughters posses their fathers' X-chromosome). • No male children of an affected father will be affected (sons do not inherit their fathers' X-chromosome).
Examples:
• Lesch-Nyhan Syndrome • Duchene Muscular Dystrophy • Hunter's Disease • Menkes Disease (Kinky hair syndrome) • Glucose 6 Phosphate Dehydrogenase Deficiency • Hemophilia A and B • Fabry's Disease • Wiskott-Aldrich Syndrome • Bruton's Aggamaglobulinemia • Color Blindness • Complete Androgen Insensitivity • Congenital Aqueductal stenosis (hydrocephalus) • Inherited Nephrogenic Diabetes Insipidus