Chap 8- Identifying disease genes

Question 1

monogenic

Answer 1

influenced by one mutation

Question 2

oligogenic

Answer 2

decided by mutations in a few genes

Question 3

polygenic

Answer 3

very complex disorders decided by mutations in multiple genes and other factors

Question 4

genetic risk factor

Answer 4

• put you at risk for developing certain diseases

- aka susceptibility factors

Question 5

protective factors

Answer 5

factors that can protect us from developing certain diseases/ lower diseases susceptibility

Question 6

what are the general types of genetic testing done?

Answer 6

• screenings- usually in pregnant mothers, newborns, or carriers
• diagnostic tests
• prediction tests- usually in asymptomatic people who have familial risk

Question 7

How do you evaluate a genetic test?

Answer 7

• ACCE
• Analytical validity
• Clinical validity
• Clinical utility
• Ethical validity

Question 8

sensitivity

Answer 8

• proportion of all people who have the disease who are correctly identified as such
• picking up true positive

Question 9

specificity

Answer 9

• proportion of all people who do not have the condition and who are correctly identified as such
• picking up true negative

Question 10

ethical considerations with genetic testing

Answer 10

• consent for genetic testing
• sharing of genetic info
• confidentiality of test results

Question 11

right to an open future principle

Answer 11

• disclosure of any genetic info from test could infringe on a child’s future autonomy

Question 12

what is 3 person IVF treatment

Answer 12

• baby born from mother who has mitochondrial disorder, father, and a mother egg donor
• take anucleated egg from mother with mitochondrial disorder and fertilize it with sperm
• take nucleus from donor egg and use it in fertilized egg
• approved only in UK

Question 13

pyrosequencing

Answer 13

• sequential enzyme reaction that detects pyrophosphate when nucleotide is added to DNA
• can be used to determine mutant and normal sequences
• helpful in heterogeneous tumor samples

Question 14

chromosome FISH

Answer 14

• FISH= fluorescence in situ hybridization
• higher resolution than karyotyping
• fix chromosomes, treat them to denature DNA, insert fluorescently labeled probes
• location of probes recorded
• cells rested in metaphase
• helps to identify more specific mutations compared to karyotyping

Question 15

principle of genetic linkage

Answer 15

• alleles very closely located will travel together

- chance of being separated during recombination is very low

Question 16

what is the LOD score?

Answer 16

• chance that genes will be inherited together

- if score is 3 or higher, genes are close together and will likely be inherited together

Question 17

restriction fragment length polymorphism (RFLP)

Answer 17

• used to map genes to defined subchromosomal regions
• similar to mini and micro satellites
• restriction enzymes cut DNA at specific sites
• run fragments on the gel to identify someone (everyones cuts will look different)

Question 18

exome sequencing

Answer 18

• widely used to identify rare diseases
• exome- all exons in genome
• introns are disposed of and sequence only the exons
• very cost effective and fast

Question 19

phenocopy

Answer 19

• diseases that closely mimic phenotype but do not have genotype commonly associated with disease

Question 20

Genome-Wide Association Studies (GWAS)

Answer 20

• studies conducted in huge populations
• look for SNPs associated with certain complex diseases
• allows for better strategies to detect, treat, and prevent disease

Question 21

GWAS and Inflammatory Bowel Disease

Answer 21

• succesful in identifying genes for Crohn’s and ulcerative colitis
• in both cases disease resulted from abnormal immune response to intestinal microbiota
• autophagy process dysregulation

Question 22

heat maps

Answer 22

• show how strongly diseases are associated with each other
• compare genetic profiles of different diseases
• strong associations are indicated by 95 or higher

Question 23

FUT2 allele

Answer 23

• codes for fucosyltransferase enzyme
• mutation makes person immune to norovirus
• makes them mores susceptible to Crohn’s and type 1 diabetes
• FUT2 is required for norovirus to invade cells, but mutation causes change in microbial flora -> Crohn’s

Question 24

epistasis

Answer 24

• interaction between 2 or more genes to control a single phenotype
• genes that belong to same biological pathway are likely to interact

Question 25

endophenotype

Answer 25

• behavioral component of diseases
• i.e. have a gene type that makes a person overeat
• due to overeating they are at a higher risk for diseases associated with obesity

Question 26

case control studies

Answer 26

• most widely used for studying genetic and environmental factors of complex diseases
• usually retrospective
• depend on recall which introduces hugh personal bias

Question 27

cohort studies

Answer 27

• prospective
• best to identify role of environment in disease process
• study individuals over long time before onset of disease

Question 28

what is the thrifty phenotype

Answer 28

• adaptation of fetus that maximizes chance of surviving in environment with limited nutrition
• in adult life the person has altered metabolism
• when food is readily available they are more likely to develop type 2 diabetes, obesity, and HTN