lecture 20- mapping disease through mendelian approaches

Question 1

human genome project

Answer 1

launched in 1990 to sequence the first complete human genome

Question 2

massive parallel methods (next gen sequencing)

Answer 2

revolutionizing sequencing providing faster and cheaper genomes

Question 3

genome centers

Answer 3

operate highly automated production lines, increasing genomic output

Question 4

snp (single nucleotide polymorphisms)

Answer 4

places where 1 base pair is different (changes amino acids, changes protein)
ex: glutamic acid to valine causes sickle cell

Question 5

short tandem repeats (genetic markers)

Answer 5

regions in the genome where there are many repeats
ex: over 30 CAG repeats- huntington (repeats are likely to make mutations because there are so many similar things)

Question 6

copy number variants

Answer 6

long region of the genome where you may have different numbers of copies
ex: alpha thalassemia

Question 7

cystic fibrosis

Answer 7

Cystic fibrosis (CF) is a genetic disorder that causes problems with breathing and digestion. CF affects about 35,000 people in the United States. People with CF have mucus that is too thick and sticky, which. blocks airways and leads to lung damage; traps germs and makes infections more likely

each person has a gene called
CFTR. That gene encodes a protein that functions as a channel that
allows chloride ions to travel across cell membranes. When a mutation
occurs that inactivates the CFTR gene, the protein no longer performs its
function, causing improper ion concentrations inside and outside their
cells. Thus, a person with CF does not properly produce sweat, digestive
juices, and mucus.

Question 8

breakthroughs in diagnosis and etiology of cf

Answer 8

Question 9

cftr (cystic fibrosis gene)

Answer 9

Question 10

How many genes do we have

Answer 10

20,000

Question 11

mendelian genetics approach to disease mapping

Answer 11

uses small datasets to investigate single gene/simple traits

Question 12

population genetic approach to disease mapping

Answer 12

uses large datasets to investigate complex traits

Question 12

why cant qtl mapping be done in humans

Answer 12

cant ethically do a backcross or intercross unlike fruit flies

Question 13

steps of a linkage analysis study

Answer 13

Question 14

STR (short tandem repeats)

Answer 14

useful for linkage analysis as they are highly polymorphic

Question 15

how do we genotype strs

Answer 15

by measuring length of dna bands with gels after pcr

Question 16

why can bi-allelic markers sometimes lead to uninformative crosses

Answer 16

Question 17

steps of a lod score calculation

Answer 17

Question 18

informative parent

Answer 18

heterozygote (assuming pedigree is informative) for both the trait and the marker

*other parent must be homozygous

Question 19

phase

Answer 19

the arrangement of trait and marker alleles (which allele combinations are present on each homolog in the parents alleles)

Question 20

lod score

Answer 20

measures the likelihood that each dna site being tested is linked to the site responsible for the disease

Question 21

calculating lod score

Answer 21

Question 22

Autosomal dominant

Answer 22

Autosomal dominant is a pattern of inheritance characteristic of some genetic disorders. “Autosomal” means that the gene in question is located on one of the numbered, or non-sex, chromosomes. “Dominant” means that a single copy of the mutated gene (from one parent) is enough to cause the disorder.

Question 23

The key components of disease mapping using LOD score analysis are as
follows

Answer 23

1. Pedigrees (generated in hospitals): Choose a family and determine
   whether each person has the disease or not
2. Genotyping (performed in labs): Determine which allele each
   person has at many sites (marker loci) in the genome
3. LOD score calculations (performed using computers): Identify the
   site that is most correlated with presence/absence of the disease

Question 24

benefits of using str as marker

Answer 24

A benefit of using STRs is that they tend to be very variable; therefore, many different alleles are possible. This means that it is very likely that any individual in a pedigree will be heterozygous at the STR locus. This makes it easier to track inheritance of a specific allele throughout the pedigree. If the parents are both heterozygous, we can say with confidence which allele each child inherited from each parent. If the parents are homozygous, it becomes unclear which allele they passed on to each child, making the site less informative.

Question 25

A LOD score less than 0 indicates

Answer 25

that the marker and locus of interest are more likely to be assorting independently than they are to be linked at the tested recombination frequency. Note that this does not necessarily mean that they are not linked, only that they are not likely to be linked at the recombination frequency that you tested

Question 26

what does the marker that gives the highest LOD score tell us

Answer 26

where to look for our site of interest