9 22 Genetics Consiguity-Table 1 Flashcards
when does inactivation occur in the cells of a female?
at about the 10-20 cell stage
why would a female manafest an x-linked recesive disease?
they may have enough of the normal x chromosome inactivated to make it not a clear 50 50 split and they may express some of the disease traits
how do we estimate the allele frequency (gene frequency) for x-linked recessive disease?
take the prevalence in males, and this is equal to the allele frequency (q).
how do we find the frequency of a x-linked disease in females?
predict the gene frequency (q) using the prevelence in males and then for females use q*q or the prevelence squared.
what causes hemophelia?
factor VIII deficiency: hemophilia A; factor IX deficiency: hemophilia B
why would a father never pass red-green colorblindness onto a son?
it is an x-linked recessive trait.
what is the phenotype for hemophilia A?
clotting time is increased; bruising, hemorrhage; hemarthrosis (bleeding into the joints)
how could we genetically treat hemophelia?
AAV vecotor injected into peripheral vein to activate factor gene activity
what is Duchenne muscular dystrophy?
it is the most common form of muscular dystrophy and one of the most deadly form of muscluar dystrophy – due to lack of dystrophin to connect the actin fibers to the intermembrane components and to the components outside of the cell.
what are some early signs of duchenne muscular dystrophy?
gowers sign (climb up the legs to stand up); proximal wasting pseudohypertrophy of the muscles.
what are some late stage signs of duchenne?
severe muscle wastage, elevated creatine kinase; invovlement of cardiac and respiraotory muscles, decreased average IQ
what are two experimental therapies for Duchenne?
ribosomal readthrough with PTC124 skips the premature stop codon. 2. Exon skipping
what is the genetic cause of duchenne?
2/3 of the mutations in DMD gene are deletions or insertions that cause frame shift mutations.
what would occur if you have a dystrophin altered by a reading frame instead of deleted by a non-sense mutation like DMD
You would get Becker muscular dystrophy, which is a slower form of the disease.
what identifies a pedigree as X-linked dominant?
male-male transmission is not seen; heterozygous females are affected; affected females seen twice as often as affected males, on average; disease phenotype seen in multiple generations; skipped generations unusual.
what are the recurrence risks for X-linked dominant and recessive inheritance?
know how to do the punnet squares
the proportio of genes shared by a pair of relatives
the Coefficient of relationship!
how to determine coefficient of relationship
look at the prob. of offspring getting a specific allele at each generation. generally it will be a one half chance (two parents) and so each step in the family tree that connects them adds another 1/2 prob. then if we want a specific shared gene use the ‘and’ rule of prob. and mutliply all of the 1/2 factors. Then account for two shared grandparents by multiplying that by two.
what proportion of DNA is shared with a first cousin?
1/8 – prob. that same gene makes it through two generations is 1/2^4 ; then times by two to account for two shared grandparents!
the coefficient of relationship for 2nd cousin mating
1/32
what does the coefficient of relationship mean for cousins?
they have that fraction of DNA that is completely identicle
how to find the prob. of affected offspring in first cousin mating?
coefficint of relationship (1/8) times the prob. of producing affected offspring if they are both carriers (1/4) (from a punnet square for a recessive gene) therefore= 1/32.
Prob. of affected offspring with affected homozygous individual as a parent
(1/8+1/8)(coefficient of relationship) * 1/2 (prob. of having affected offspring from a punnit square)
what results with close consiguity?
excessive homozygosity
how does consanguinity increase the prob. of affected offspring?
from a pop. based prob. of the diseaase, in consanguinity the prob. just becomes the coefficient of relationships
what is the change in chance of genetic diseases arising at all in consanguinity?
about twice as high in 1st degree cousins
