X-linked inheritance

Question 1

X-inactivation

Answer 1

also called lyonisation
one of the X copies of a female is inactivated
silenced X-chromosome stored as heterochromatin
prevents double X-chromosome products in females compared to males
inactivation by random choice
will remain inactive for lifetime of person

Question 2

duchenne muscular dystrophy

Answer 2

weakness mainly in proximal muscles, particularly in the trunk, hips and shoulders
fine movements less affected than eg walking
causes shortage of dystrophin in the muscles, which leads to muscle fibre damage and weakness

65% of cases caused by intragenic deletions

Question 3

dystrophin

Answer 3

located between the sarcomere and the outermost layer of myofilaments in the muscle fibre
cohesive protein that links actin filaments to support proteins within the sarcolemma
this means that is supports muscle fibre strength

Question 4

X-linked inheritance

Answer 4

it is impossible for a father to pass on X-linked condition to son

Question 5

mosaic inactivation

Answer 5

depends on which X-chromosome is expressed
the higher the proportion of affected cell, the higher the penetrance. this is true of x-linked conditions
in x-linked, with a lower x-expression, all males will be affected. females will increase in phenotype expression as the proportion of affected X chromosome increases

in gonadal mosaicism, maternal X passed on can be either normal or affected. the higher the number of cells expressing one X-chromosome, the more likely they will be passed on, and male offspring will be affected. the mother will only be affected depending on the level of expression

Question 6

duchenne

Answer 6

1/3 of males affected are de novo mutations
therefore of affected males, 2/3 will inherit the condition from their mother
out of frame deletions are associated with a more severe form of the disease than in frame mutations

Question 7

imprinted genes

Answer 7

preferentially express maternal or paternal gene SDHD
consistently done in almost every cell. a gene is inactivated by methylation
in familial paragangliomas, maternal copies are always methylated. so a daughter who inherits paternal DNA will methylate this when an egg is formed
a son will demethylate a maternal copy during sperm production. his copies will be methylated so he is safe, but de-methlyated copies will be present in the sperm so can be passed on, regardless of whether offspring is male or female (most of the time)
only de-methylated copies will express the tumour suppressor dominant gene. can therefore be a carrier of a dominant disorder

Question 8

germline epigenetic modification

Answer 8

eg as seen in paragangliomatosis

Question 9

germline imprinting disorders

Answer 9

prader wili/angelman syndrome
beckwith wiedemann syndrome
russel-silver syndrome

Question 10

somatic imprinting abnormalities in colon cancer

Answer 10

important in non-heritable disease
random hypermethylation of the promoter of MLH-1
this inactivates MLH-1, leading to a tumour that looks the same as a heritable colon cancer

Question 11

genomic imprinting

Answer 11

inheritance independent of mendelian inheritance
involves histone and genetic methylation without altering the genetic code, leading to silencing of certain genes
linked to the parent of origin of the genetic material