Sex Linked Inheritance  

Introduction

• A human female, has 23 pair of chromosomes

• A human male, has 22 similar pairs and one pair consisting of two chromosomes that are dissimilar in size and structure.

• The 23 rd pair in both the sexes is called sex chromosomes

• the female, XX. the male, XY

X-linked diseases

• X-linked diseases are those for which the gene is present on the X chromosome.

• X-linked diseases show inheritance patterns that differ from autosomal diseases.

• This occurs because males only have one copy of the X chromosome (plus their Y chromosome) and females have two X chromosomes.

• Because of this, males and females show different patterns of inheritance and severity of manifestation. While there are both dominant and recessive X-linked diseases, there are some characteristics that are common to X-linked disorders in general

• X-linked genes are never passed from father to son.

• The Y chromosome is the only sex chromosome that passes from father to son.

• Males are never carriers – if they have a mutated gene on the X chromosome, it will be expressed.

• Males are termed hemizygous for genes on the X chromosome.

 

X-linked dominant • hereditary pattern in which a dominant gene on the X chromos

ome causes a characteristic to be manifested in the offspring.

• X-linked dominant diseases are those that are expressed in females when only a single copy of the mutated gene is present.

• Very few X-linked dominant diseases have been identified (e.g. hypophosphatemic rickets, Alport syndrome, diabetes insipidus)

hypophosphatemic rickets or vitamin D resistant rickets >>>low serum phosphorus, skeletal abnormalities

• Alport syndrome, which involves progressive hearing loss and progressive kidney problems.

Characteristics of X-linked dominant diseases include:

• Never passed from father to son.

• Affected males produce only affected females. An affected male only has one X chromosome to pass on to his daughters

• Affected females produce 50% normal and 50% affected offspring.. >>>> heterozygous

• Males are usually more severely affected than females. Some X-linked dominant traits may even be lethal to males.

• Females are more likely to be affected. Since females have 2 X chromosomes, they have 2 “chances” to inherit the mutated allele.

Pattern for inheritance• Mating A Mating B

Pattern for inheritance• Mating A Mating B

Amelogenesis Imperfecta-1

: X-linked dominant

Gene name: Amelogenin, Chromosome location: Xp22.3-p22.1

Altered Cellular function: Abnormal tooth enamel

Symptoms: Very hard enamel, thin enamel, small teeth, and/or rough teeth

Incidence: Rare

X-linked recessive

• hereditary pattern in which a recessive gene on the X chromosome results in the manifestation of characteristics in male offspring and a carrier state in female offspring

• X-linked recessive diseases are those in which a female must have two copies of the mutant allele in order for the mutant phenotype to develop.

• Many X-linked recessive disorders are well-known, including color blindness, hemophilia, and Duchenne muscular dystrophy.

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Pattern of x linked recessive inheritance

Hemophilia

• The blood fails to clot normally• Lacking a blood clotting factor

VIII(antihemophilic globulin, AHG),IX• bleeding from even minor cuts• in 1,500 newborn males. Most (75%) have he

mophilia A, a lack of clotting factor VIII. • Hemophilia B- "Christmas Disease" is a defect in

clotting factor IX.• Transfusions of fresh whole blood or plasma or f

actor concentrates control bleeding

Inheritance of hemophilia

f

Typical features of X-linked recessive inheritance

• Never passed from father to son.

• Males are much more likely to be affected because they only need one copy of the mutant allele to express the phenotype.

• • Affected males get the disease from their mothers and all of the

ir daughters are obligate carriers.

• Sons of heterozygous females have a 50% chance of receiving the mutant allele.

The Marker X syndrome

• Fragile X syndrome (Marker X syndrome ) is a genetic condition involving changes in the long arm of the X chromosome. It is characterized by mental retardation.

Alternative Names Martin-Bell syndrome; Marker X syndrome

Causes, & Risk Factors

• Fragile X syndrome is the most common form of inherited mental retardation in males and a significant cause in females.

• The inheritance is different from common dominant or rece

ssive inheritance patterns.

• A fragile area on the X chromosome tends to repeat bits of the genetic code.

• The more repeats, the more likely there is to be a problem.

• Boys and girls can both be affected, but because boys have only one X chromosome, a single fragile X is more likely to affect them more severely.

Fragile X Syndrome Symptoms & Signs

• Family history of fragile X syndrome, especially a male relative

• Mental retardation • Large testicles (macro-orchidism) • Large size • Tendency to avoid eye contact • Hyperactive behavior • Large forehead and/or ears with a prominent jaw

Fragile X Syndrome Symptoms

• Sex-limited inheritance:• A trait that appears in only one sex is called sex-limited. • This is different from X-linked inheritance, which refers to

traits carried on the X chromosome. • Sex hormones and other physiologic differences betwee

n males and females may alter the expressivity of a gene.

• For example, premature baldness is an autosomal dominant trait, but presumably as a result of female sex hormones, the condition is rarely expressed in the female, and then usually only after menopause.

• Thus, sex-limited inheritance, perhaps more correctly called sex-influenced inheritance, is a special case of limited expressivity and penetrance

Sex limited traits

• sex linked traits are generally expressed much more often in males than in females.

• some traits which affect one sex more than another are not necessarily sex linked.

• Examples are cases of sex limited expression which might include genes affecting beard growth or breast size, and (in cattle), horn growth and milk yield.

Sex-influenced traits

• characteristic may appear in both sexes but expression of the phenotype differs.

• Example: Early balding (pattern baldness) in humans. Heterozygous men (b+/b) lose their hair; heteroyzgous women do not have significant hair loss.

• Homozygous men or women (b/b) become bald. The trait is therefore dominant in men, recessive in women. (We used b to designate the mutant baldness allele even though the allele is dominant in males.)