Human genetics 4 Flashcards
(23 cards)
What are single gene disorders?
Disorders caused by alterations of a single gene
What are complex disorders?
- disorders caused by multiple genes and the interactions they have with the environment
- cause of premature mortality in almost 2/3 of all individuals
- usually less severe than single gene disorders
- many have a genetic component(s)
- inheritance would not follow mendelian pattern
What are dizyogtic twins?
- are no similar than siblings
- 2 sperm fertilize 2 eggs
- 50% of alleles at all loci
- like siblings
- however, they also share the same uterine environment
What are monozygotic twins?
- are almost genetically identical
- 1 sperm fetilizes 1 egg
- cleavage follows
- 100% of alleles in common (in theory)
What is concordance?
Do the twins share any traits?
What is discordance?
What traits do they don’t share?
What does discordance tell us in twin studies
- any discordance between monozygotic twins (less than 100% concordance) is strong evidence that non-genetic factors play a role in the trait
Concordance of mono vs dizygotic twins
- MZ and same-sex DZ share common intrauterine environment, sex and environmnet during childhood
- comparision of concordance for a disease between MZ and same-sex DZ twins eliminates (reduces) environmental factors
- 100% of genes in commonvs 50% of genes in common
- greater concordance in MZ twins is strong evidence for genetic component
What types of studies can we conduct with MZ twins who are separated at birth
- can observe identical genotypes reared in different environments
- psychiatric disorders
- stong environmental influences thought to play a role
- must always interpret with care
What does it mean to interpret twin studies with care?
- not entirely identical genome (MZ twins)
- different gene expression - epigenetics
- intrauterine environment
- somatic alterations during development - antibodies
- random X inactivation in females
- environmnetal exposure
- increases with age
- ascertainment bias
Adoption studies
- compare a characteristic between children, biological and adoptive parents
- biological parents share genetics
- adoptive parents share environment
Genetic testing based on family history
- a persons geneome is “shared” with relatives
- relatives also (often) share environmental factors
- risk determines if an individual should be tested
- someone with a family history of colon cancer should be tested at an earlier age
What are the criteria for effective screening?
- clinical validity
- clinical utility
What is clinical validity?
- the extent to which a test is predictive for a disease
- what are the chances of false positives/negatives?
What is clinical utility?
- degree to which test results will alter the treatment an individual reveives
- medically and economically
What does newborn screening looks like?
- analysis of blood with mass spectroscopy
- detection of a number of disorders
- genetic tests for individual disorders
- clinical validity
- disease where early intervention is important
- clinical utility
Screening for carriers of mendelian disorders
- individuals who are healthy but have substantial risk (25%) for having children with severe autosomal recessive or X-linked illness
- focus on specific ethnic groups with high frequency (CFTR in caucasians)
- testing with a basic panel of the 23 most common mutations
- identify 88% of all CF carriers
What are different things to consider about the validity of a screen for susceptibility vs one for a single gene disorders?
- how much risk does a particual variant contribute the phenotypes as a whole?
- can it be used in a predictive fashion?
Screening for susceptibility to disease
- predictive value depends on genotype frequency, relative risk and disease prevalence
Direct to consumer testing
- most of the big companies use a SNP chip for analysis
- ancestry based on 1000 genomes variation
- “medically relevant” information based on association between disease and SNPs
What is single nucleotide polymorphism screening?
- labelled DNA applied to array
- all common SNPs in a genome can be assessed on a single chip
What is personalized genetic medicine?
- small molecule (drug) therapies that can increase protein funciton
- example used is Ivacaftor
What does Ivacaftor do in terms of treatment at the protein level?
- can increase chloride ion transport in some CFTR mutations which are properly positioned in membrane
- can open channel
- the addition of ATP can open the channel even more
