Genetics Haemophilia

x-linked recessive inheritance

females possess 2 x-chromosomes, males have 1 x , 1 y-chromosome. since mutations causing disease x-linked recessive, female carrying defect on 1 of x-chromosomes may not affected it, equivalent allele on other chromosome should express produce necessary clotting factors, due x inactivation. however, y-chromosome in male has no gene factors viii or ix. if genes responsible production of factor viii or factor ix present on male s x-chromosome deficient there no equivalent on y-chromosome cancel out, deficient gene not masked , disorder develop.

since male receives single x-chromosome mother, son of healthy female silently carrying deficient gene have 50% chance of inheriting gene , disease; , if mother affected haemophilia, have 100% chance of being haemophiliac. in contrast, female inherit disease, must receive 2 deficient x-chromosomes, 1 mother , other father (who must therefore haemophiliac himself). hence haemophilia far more common among males females. however, possible female carriers become mild haemophiliacs due lyonisation (inactivation) of x-chromosomes. haemophiliac daughters more common once were, improved treatments disease have allowed more haemophiliac males survive adulthood , become parents. adult females may experience menorrhagia (heavy periods) due bleeding tendency. pattern of inheritance criss-cross type. type of pattern seen in colour blindness.

a mother carrier has 50% chance of passing faulty x-chromosome daughter, while affected father pass on affected gene daughters. son cannot inherit defective gene father. recessive trait , can passed on if cases more severe carrier.genetic testing , genetic counselling recommended families haemophilia. prenatal testing, such amniocentesis, available pregnant women may carriers of condition.

as genetic disorders, of course possible human acquire spontaneously through mutation, rather inheriting it, because of new mutation in 1 of parents gametes. spontaneous mutations account 33% of cases of haemophilia a. 30% of cases of haemophilia b result of spontaneous gene mutation.

if female gives birth haemophiliac son, either female carrier blood disorder or haemophilia result of spontaneous mutation. until modern direct dna testing, however, impossible determine if female healthy children carrier or not. generally, more healthy sons bore, higher probability not carrier.

if male afflicted disease , has children female not carrier, daughters carriers of haemophilia. sons, however, not affected disease. disease x-linked , father cannot pass haemophilia through y-chromosome. males disorder no more pass on gene children carrier females, though daughters sire carriers , sons father not have haemophilia (unless mother carrier).

severity

there numerous different mutations cause each type of haemophilia. due differences in changes genes involved, people haemophilia have level of active clotting factor. individuals less 1% active factor classified having severe haemophilia, 1-5% active factor have moderate haemophilia, , mild haemophilia have between 5-40% of normal levels of active clotting factor.