lecture 20- mapping disease through mendelian approaches Flashcards

1
Q

human genome project

A

launched in 1990 to sequence the first complete human genome

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2
Q

massive parallel methods (next gen sequencing)

A

revolutionizing sequencing providing faster and cheaper genomes

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3
Q

genome centers

A

operate highly automated production lines, increasing genomic output

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4
Q

snp (single nucleotide polymorphisms)

A

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

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5
Q

short tandem repeats (genetic markers)

A

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)

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6
Q

copy number variants

A

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

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7
Q

cystic fibrosis

A

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.

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8
Q

breakthroughs in diagnosis and etiology of cf

A
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9
Q

cftr (cystic fibrosis gene)

A
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10
Q

How many genes do we have

A

20,000

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11
Q

mendelian genetics approach to disease mapping

A

uses small datasets to investigate single gene/simple traits

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12
Q

population genetic approach to disease mapping

A

uses large datasets to investigate complex traits

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12
Q

why cant qtl mapping be done in humans

A

cant ethically do a backcross or intercross unlike fruit flies

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13
Q

steps of a linkage analysis study

A
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14
Q

STR (short tandem repeats)

A

useful for linkage analysis as they are highly polymorphic

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15
Q

how do we genotype strs

A

by measuring length of dna bands with gels after pcr

16
Q

why can bi-allelic markers sometimes lead to uninformative crosses

A
17
Q

steps of a lod score calculation

A
18
Q

informative parent

A

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

*other parent must be homozygous

19
Q

phase

A

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

20
Q

lod score

A

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

21
Q

calculating lod score

A
22
Q

Autosomal dominant

A

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.

23
Q

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

A
  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
24
Q

benefits of using str as marker

A

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.

25
Q

A LOD score less than 0
indicates

A

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

26
Q

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

A

where to look for our site of interest