single gene disorders

Question 1

Forward vs reverse genetics

Answer 1

forward genetics: from phenotype to gene (use a disease and use likage studies and positional cloning to find the gene) Positional cloning: find genes of unkown function by mapping them relative to a gene or marker that you can clone and then walkng down the chromosome to the desired gene

Reverse genetics: from gene to phenotype (artificially mutate a gene determine effect on phenotype)

Question 2

Single gene disorders

Answer 2

mutation of a single gene is necessary and sufficient to cause disease (disease severity can be affected by the genotype or other genes)

Question 3

linkage analysis

Answer 3

Pedigree and linkage between genetic markers and occurence of the disorder. linkage is a function of distance between loci and recombination
steps involved in linkage analysis: Collect DNA from a large pedigree, genotype all individuals 300 markers, statistical analysis to determine which region of the genome is linked to the disease, best suited for singe gene disorders

Question 4

Cystic fibrosis

Answer 4

Classic : sever with pancreatic insufficiency and liver disease, no functional CFTR
Non classic: non severe
most frequent lethal disease of childhood
IDd using RFLPs

Seen in the CFTR gene (seen in all affected tissues)

CFTR is a conductance regulator for a chloride channel, mutated leads to an altered chloride balance

its a missing F 508

tests: newborn, sweat, and genotyping

Question 5

Huntingtons disease

Answer 5

rare, neurodegenerative disease, pt dies within 17 years of symptoms. huntingtin is the disease causing gene, gene spans 180 kb of genomic sequence with 67 exons. gene widely expressed in multiple tissues. Repeat of CAG in the coding region (>37 –>hd) the more repeats the the earlier the onset

Gene plays a role in protein trafficking ant neuronal stuff, loss of norma protein and gain of mutant nunting ton contribute to the disruption of multiple intracellular pathways. CAG repeats form tract

Early onset HD is more frequently inherited by father

its an autosomal dominant disease with modifier gene, genomic imprinting anticipation on chromosome 4

Question 6

Trinucleotide repeat expansion diseases

Answer 6

HD, fragile x, kennedy myotonic dystophy. All disorders are dominant and affect the brain. have genetic anticipation

Question 7

prader willi and angel man

Answer 7

heterozygous deletion 15q11, if the deletion is inherited from mom its Angel

if from dad its Prader willi