Lecture 11-12

Question 1

What are the laws of inheritance?

Answer 1

Segregation, independent assortment, linkage, and recombination

Question 2

What are the two hypothetical ways for gene X to activate gene Z?

Answer 2

X activates Y which activate Z, vs X inhibits Y, which is an inhibitor for Z

Question 3

What is epistasis?

Answer 3

When the expression of one gene can effect the expression of another (i.e. repression, inhibition)

Question 4

What is the normal function of ced-3 and ced-9, and what is their relationship genetically?

Answer 4

In ced-9 mutants, all cells undergo apoptosis. Ced-9 protects cells from death, while ced-3 promotoes cell deaht. However, in ced-3/ced-9 double mutants, no cells die. Ced-9 normally inhibits ced-3 (which normally causes call death)

Question 5

What are penetrance and expressivity (general)?

Answer 5

Terms that describe how a phenotype is expressed. A trait can be affected by an individual’s genetic background.

Question 6

What is penetrance?

Answer 6

Penetrance is the percentage of the population with the genotype that shows the trait?

Question 7

What is expressivity?

Answer 7

Expressivity is the degree to which a trait is manifested in an individual

Question 8

What are some ways to forward genetic screen?

Answer 8

Mutagenize males (x-ray radiation, mutagens, transposons) to create mutations, and mate to wild type (+/+) females. Mate F1 mutants with wild type animals. Establish individual F2 mutant colonies. F2 sibling cross, backcross to F1, or other crosses SLIDE 11 OH

Question 9

What does it mean for an allele to be hypomorphic?

Answer 9

A mutant allele with reduced gene activity is called “hypomorphic,” meaning it is marginally functional

Question 10

What is linkage mapping?

Answer 10

Also known as genetic mapping. A way to identify a mutated or disease gene. Linkage mapping aims to find a common inheritance pattern between between chromosomal region/marker and a disease phenotype. Requires genotyping on large, multi-generation pedigrees.

Question 11

How did scientists find the ob and db gene using linkage mapping?

Answer 11

Mated mice with very different genetic markers to introduce the markers to the chromosome region with the disease gene through meiosis. Scientists then find markers co-segregating the most with the phenotype (closest to the disease gene)

Question 12

Which enzymes are often used in linkage mapping and why?

Answer 12

Restriction enzymes (as part of southern blot). Easier to isolate/identify certain genes from a small fragment of DNA

Question 13

What is a helpful tool for linkage mapping?

Answer 13

Multi generation pedigree

Question 14

Why is linkage analysis harder for complex traits (involving multiple genes)?

Answer 14

The relationship between phenotype and genotype is not as clear

Question 15

How do scientists study more complex traits?

Answer 15

Association mapping

Question 16

What is association mapping?

Answer 16

Looks at common inheritance, but in populations of unrelated individuals (no pedigrees needed). Uses fine mapping with many closely spaced markers. Can be use din conjunction with linkage mapping. When used with genome wide map of markers, called genome wide association study (GWAS)

Question 17

What is linkage disequilibrium?

Answer 17

The non-random association of alleles at two or more loci that descend from single ancestral chromosome

Question 18

What are snp?

Answer 18

Single nucleotide polymorphisms. Substitution of a single nucleotide at a specific position in the genome that is present in a sufficiently large fraction of the population (1% or more)

Question 19

How is GWAS conducted?

Answer 19

Sequence genome of those who are affected, and a control group (unaffected). Try to figure out if the polymorphic marker is responsible for the trait.

Question 20

How are different SNPs detected?

Answer 20

An array containing immobilized allele specific oligonucleotide probes. Fragmented DNA of a target, labeled with fluorescent dyes. A detection system records and interprets the hybridization signal.

Question 21

Why is GWAs not always feasible, and how can we maximize feasibility?

Answer 21

Not feasible: Identify all 10 million common SNPs, collect 1000 cases and controls, genotype all DNAs for all SNPs –> 20 billion genotypes (billions of dollars per disease
More feasible: Identify set of 300K tag SNPs, collect 1000 cases and controls, genotype all DNAs for all SNPs –> 600 million genotypes (600K per disease)

Question 22

What is a tag SNP

Answer 22

A representative SNP ina. region of the genome with high linkage disequilibrium representing a group of SNPs that are inherited together (haplotype)

Question 23

What is the HapMap and how is it constructed?

Answer 23

HapMap is a project to develop a haplotype (inherited polymorphisms) map. Genomes from different individuals are sequenced. SNP regions are isolated and put compared to identify tag SNPs within haplotypes (so that each haplotype can be uniquely identified without having to examine all co-inherited SNPs)

Question 24

What is a haplotype?

Answer 24

Adjacent SNPs that are inherited together

Question 25

How is GWAS a helpful tool, and what are some drawbacks?

Answer 25

It can robustly identify genetic association with disease. It only identifies regions of association. How loci interact to influence phenotype is poorly understood, and the majority of genetic variance for common complex diseases remains unexplained.