Sex linkage
Encyclopedia
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 mammal
s, the female is the homozygous sex, with two X chromosome
s (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).
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.
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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 posses 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
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
expression of an allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
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 mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s, the female is the homozygous sex, with two X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
s (XX), while the male is heterozygous, with one X and one Y chromosome (XY). Genes on the X or Y chromosome
Y chromosome
The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...
are called sex linked genes.
In birds, the opposite is true: the male is the homozygous sex, having two Z chromosomes
ZW sex-determination system
The ZW sex-determination system is a system that determines the sex of offspring in birds, some fish and crustaceans such as the giant river prawn, some insects , and some reptiles, including Komodo dragons...
(ZZ), and the female (hen) is heterozygous, having one Z and one W chromosome (ZW).
Linkage overview
X-linked recessiveX-linked recessive
X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males and in females who are homozygous for the gene mutation X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on...
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
Reciprocal cross
In genetics, a reciprocal cross is a breeding experiment designed to test the role of parental sex on a given inheritance pattern. All parent organisms must be true breeding to properly carry out such an experiment. In one cross, a male expressing the trait of interest will be crossed with a...
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 . |
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 posses 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
Sex-linked traits in other animals
- Calico or tortoiseshell catTortoiseshell catTortoiseshell describes a coat coloring found mostly in female cats. Cats of this color are mottled, with patches of orange or cream and chocolate, black or blue. They are sometimes called torties...
s, which have orange-and-black fur - WhiteWhite (mutation)White, abbreviated w, was the first sex-linked mutation ever discovered in the fruit fly Drosophila melanogaster. In 1910 Thomas Hunt Morgan, collected a single male white-eyed mutant from a population of Drosophila melanogaster fruit flies, which usually have bright red eyes...
eyes in Drosophila melanogasterDrosophila melanogasterDrosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
flies—the first sex-linked geneGeneA gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
ever discovered