GM 02: Genetic Basis of Disease Flashcards
The entire human species shares (X)% of our genomes. The thought is that the main sources of variation come from (Y).
X = 99.5 Y = SNPs (single NT polymorphisms)
What are SNPs?
Loci on genome where sequence varies at position of a single NT
Most SNPs in human genome are found in which region of the gene?
Exon
Alternative splicing is essentially using (one/multiple) gene(s) to produce (X) that includes different combinations of (Y).
One;
X = mature mRNA
Y = gene’s exons
What’s copy number variation (CNV)?
Regions of genome that differ (from person to person) in total number of copies per genome
T/F: If proteins that carryout epigenetic modification exhibit variability, all their target genes will also demonstrate variability.
True
Define Familial Clustering.
Comparing probability of developing disorder in individual with affected relative versus member of general population
Conducting a twin study is an approach to determine which information about a disease?
If it has a genetic basis
A genetic disease would be expected to portray which results in twin study?
Higher concordance (phenotypic similarity) in monozygotic than dizygotic twins
Linkage analysis is based on the principle that:
Genes whose loci are close in proximity will be inherited together
Due to recombination, an individual will inherit a maternal chromosome that’s a combo of:
Both of their mother’s chromosomes
(X) genes, separated by large distance on chromosome, are (more/less/equally) likely to be separated by recombination event than (Y) genes.
X = unlinked;
More likely;
Y = linked
List the type of (DNA/mRNA) markers used in linkage analysis.
DNA
- RFLPs (restriction fragment length polymorphisms)
- SSLPs (simple sequence length polymorphisms)
- SNPs (single NT polymorphisms)
What are RFLPs (restriction fragment length polymorphisms)?
Loci on genome where sequences variation in population results in creation/elimination of restriction enzyme recognition site
What are SSLPs (simple sequence length polymorphisms)?
Simple sequences (such as dinucleotide repeats) can vary in length per individual
It’s important to recognize that linkage study analysis is (X), requiring a genetic model that describes:
X = parametric;
- Mode of inheritance
- Penetrance
- Gene frequency
- Number of loci involved
In order to gain enough statistical power to declare particular marker locus as significantly linked to disease locus, one needs to have:
Large pedigrees with multiple cases of affected individuals
In the method “affected sib pair analysis”, one expects siblings (by chance) to share (X) copies of their marker alleles.
X = 0, 1, or 2
In “affected sib pair analysis”, which phenomenon would been seen if a particular marker locus is linked to disease gene?
Skewing of distribution of allele sharing in affected siblings
In “affected sib pair analysis”, which phenomenon would been seen if a particular marker locus is linked to recessive disease gene?
Disproportionate number of affected siblings sharing both alleles of a marker
In “affected sib pair analysis”, which phenomenon would been seen if a particular marker locus is linked to dominant disease gene?
Disproportionate number of affected siblings sharing at least one allele of a marker
Identity by state versus descent is an issue in which method of analysis? Why?
Affected sib pair analysis;
We don’t have parental DNA information
Describe allele sharing from “identity by state”.
Both siblings carry marker because both parents have copy of the same allele for given marker locus
Identity by (state/descent) can be misleading.
State
In identity by state phenomenon, (one/both) siblings have inherited (same/different) allele at marker locus from (the same/different) parent.
Both;
same;
different
Describe allele sharing from “identity by descent”.
Affected siblings share same allele at given marker locus, inherited from the same parent
One way to improve detection of identity by (state/descent) is to use (X) as markers because they have (few/many) (Y). This makes it less likely that the parents will (Z).
Descent; X = SSLPs Many Y = alleles Z = have identical allele at a given marker locus
In linkage studies across multiple families, the same (allele/marker), but not necessarily the same (allele/marker) is inherited with the disease gene.
Marker; allele
Linkage disequilibrium (in association studies) refers to search for statistical association between (X) and (Y).
X = phenotype Y = a single allele
Linkage disequilibrium would only exist if affected individuals in population all had (X).
X = common distant ancestor
The (X) association study design has internal controls in the form of (Y).
X = transmission disequilibrium test (Tdt) Y = parental genotypes
In transmission disequilibrium test (Tdt), if marker allele is not associated with disease phenotype, what are the expected results?
Marked and unmarked allele transmitted to affected offspring with equal probability
In transmission disequilibrium test (Tdt), if marker allele is associated with disease phenotype, what are the expected results?
Marked allele will be statistically over-transmitted to affected offspring
In transmission disequilibrium test (Tdt), which markers are especially useful?
SNPs
List the major sources of human genetic variation.
- SNPs
- CNVs
- Alternative splicing
- Epigenetic modification
For autosomal dominant disorders, we tend to assume affected individual is (homo/hetero)-zygous because:
Heterozygous;
Mendelian disorders are rare
(Males/females) have greater chance of being affected, and more (mildly/severely), by X-linked dominant disease.
Females; More mildly (X-inactivation)
Locus heterogeneity is:
Phenomenon when multiple different genes can lead to similar clinical presentations
McKusick number: list first digits and mode of inheritance implied for each.
1: autosomal
2: autosomal
3: X- linked
4: Y- linked
5: mitochondrial
6: autosomal
