SEX LINKED DISEASES

any disease or abnormal condition that is determined by the sex chromosomes or by a defective gene on a sex
chromosome. Sex-linked disorders may involve a deviation in the number of either the X or Y chromosomes, as
occurs in Turner's syndrome and Klinefelter's syndrome, most occurrences of which are a result of
nondisjunction during meiosis. Such aberrations in the number of sex chromosomes do not produce the severe
clinical effects that are associated with autosomal aberrations, although they usually cause some degree of
mental deficiency. Other sex-linked disorders are transmitted by single-gene defects carried on the X
chromosome. X-linked dominant conditions, such as hypophosphatemic vitamin D-resistant rickets, are rare,
and males are more seriously affected than females. In inheritance patterns, X-linked dominant conditions are
transmitted by affected males to all of their daughters but none of their sons, by affected heterozygous females
to one half of their children regardless of sex, and by affected homozygous females to all of their children. More
common are X-linked recessive conditions, such as color blindness, ocular albinism, the Xg blood types,
hemophilia, Duchenne muscular dystrophy, and inborn errors of metabolism. Such conditions are always
transmitted by females. Those predominantly affected are males because they have only one X chromosome,
and all of its genes, whether recessive or dominant, are expressed. Occasionally, females heterozygous for X-
linked recessive disorders show varying degrees of expression, but never as severe as those of affected males.
There are no known clinically significant traits or conditions associated with the genes on the Y chromosome;
their only known function is to trigger the development of male characteristics.

A B C
X-link dominant inheritance
Each child of a mother affected with an X-linked dominant trait has a 50% chance of inheriting the mutation
and thus being affected with the disorder. If only the father is affected, 100% of the daughters will be affected,
since they inherit their father's X-chromosome, and 0% of the sons will be affected, since they inherit their
father's Y-chromosome
X-linked Dominant Diseases:
hypophosphatemia Cleft palate

X-link

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, since
males have only 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 if the father does not carry the recessive allele. All
female children of an affected father will be carriers (assuming the mother is not affected or a carrier), as
daughters possess their father's X-chromosome. If the mother is not a carrier, no male children of an affected
father will be affected, as males only inherit their father's Y-chromosome.
X-Iinked Recessive Diseases:
Color blindness Duchenne muscular dystrophy Hemophilia A and B

Y-Linked Genes:
The Y-chromosome has no corresponding locus in the X-chromosome and the mode of transmission of a Y-
linked gene is very simple. The female has no Y-chromosome, so women cannot exhibit the trait. The normal
male has only one Y-chromosome and so the gene is necessarily unpaired and, if present, it must be
expressed.So, the question of dominant or recessiveness cannot arise. The gene simply follows the path of the
Y-chromosome and so is handed on by a affected male to all his sons.The best known example of Y-linked
human gene is the growth of hair on the outer rim of the ear (trichosis) and porcupine man. The gene, present in
Y-chromosome, is also known as holandric gene. A histocompatibility gene (H-Y), however, has recently been
mapped on the short arm of the human Y-chromosome. However, one conclusion is that very few genes are
located on the human Y-chromosome and most part of the Y-chromosome is permanently hetero- chromatic.
Y-linked diseases
Azoospermia Retinitis pigmentosa
autosomal dominant disorder
An autosomal dominant disorder is expressed whether a person inherits one or two copies of the disease-causing
allele. It therefore typically appears in every generation. Because the allele is dominant and located on an
autosome, one or both of the affected individual’s parents must also have the disorder (unless the disease-
casusing allele arose by a new mutation).
autosomal recessive disorder
Inheriting an autosomal recessive disorder requires that a person receive the disease-causing allele from both
parents. Each parent must therefore carry at least one copy of allele, either because they are homozygous
recessive (and therefore have a disease) or because they are heterozygous . A person who is heterozygous is
called a carrier because he or she is unaffected by the disorder but still has a 50% chance of passing the disease-
causing allele to the next generation. If both parents are carriers, autosomal recessive conditions may seem to
disappear in one generalation, only to reappear in the next.

Pedigree charts
Pedigree charts depicting family relationships and phenotype are useful for determining a disorder’s mode of
inheritance. In a pedigree chart, squares indicate males, and circles denote females. Colored shapes indicate
individuals with the disorder, and half-filled shapes represent known carriers. Horizontal lines connect parents.
Siblings connect to their parents by vertical lines and to each other by an elevated horizontal line.
 NORMAL FEMALE

HOMOZYGOUS FEMALE

NORMAL MALE

HOMOZYGOUS MALE

A pedigree for an autosomal dominant trait; affected individuals are homozygous dominant or heterozygous.

EXERCISE
Create your own pedigree analysis and analyze it.