Flashcards in Genetics in Medicine 2 Deck (139)
What are the 3 types of mendelian inheritance?
3) X linked
What does 'complex' mean in a genetic disease sense?
Describes something with an inherited but not mendelian component
What does the term 'polygenic' mean?
the result of the action of multiple genes
What does the term multifactorial mean?
the result of multiple factors often involving genetic and environmental factors
What does lamba s refer to?
Statistic that refers to your risk of developing a condition if you have an affected sibling relative to the general population
What is familial clustering?
Refers to a condition that tends to run in families where sufferers get reoccurring headaches only on one side of the head and they can last for week
Is schizophrenia an inherited condition?
It does have an inherited component but its not mendelian, its multifactorial
What does the increased risk of developing schizophrenia if you have an affected fraternal twin compared to if you have an affected sibling suggest?
That there is an environmental component as like siblings, fraternal twins have different genotypes but share a significant environmental factor that siblings dont - a uterus
What are fraternal twins?
Non identical twins - ie. Di-zygotic twins
What does this increased risk of having schizophrenia if you have an affected identical twin compared to having an affected fraternal twin suggest?
That there is a significant genetic factor because although fraternal and identical twins share a similar environment ie a uterus etc. the difference is identical twins have the same genotype
What can a high lamba s show about a condition?
That it has a genetic component
Should a genetic disease have a higher concordance in mono zygotic or dizygotic twins?
Do cancer, hypertension, manic depression and acute infection and death have a higher concordance in MZ or DZ twins?
Cancer, hypertension, manic depression all have higher concordance in MZ twins suggesting a genetic component
Acute infection and death dont have a higher concordance in MZ twins suggesting no genetic component
What are the 2 main problems with twin studies?
1) Assumption that the degree of environmental sharing is the same for all MZ twins - can be large differences in birth weight in MZ demonstrating a different pre natal environment, variation in the time of splitting of the early embryo, diamniotic MZ twins survive better than monchorionic
2) DZ can share more than half their genes
Why are adoption studies performed, what kinds of conditions are they usually carried out for and why are they no longer carried out as often?
Child is put in different environment because of adoption
Can compare the fates of its adoptive versus biological family
Share genes but not environments with its biological parents
Share environments but not genes with its adoptive parents
Most often performed for psychiatric conditions
Adoptions are becoming rarer and there are ethical issues about contacting the biological family
Are genes dominant or recessive in multifactorial conditions?
Neither they are additive
How do traits with multifactorial inheritance tend to be distributed in the population?
Normally distributed - Gaussian, bell shaped curve
Do conditions with polygenic/multifactorial/complex inheritance tend to run in families, if so in what pattern?
Yes but not in a simple mendelian fashion
Name 6 congenital malformations with multifactorial inheritance?
1) Cleft lip/palate
2) Congenital hip dislocation
3) Congenital heart defects
5) Pyloric stenosis
Name 16 acquired diseases of childhood and adult life with multifactorial inheritance?
3) Bipolar disorder
4) Chrohn's disease
6) Parkinsons disease
15) Multiple Sclerosis
16) Rheumatoid Arthritis
Although NTDs are a congenital defect showing multifactorial inheritance, what environmental factor can significantly reduce the risk?
Maternal folic acid supplementation
50-70% of NTDs can be prevented
Roughly how does a genome wide association study (GWAS) work?
Have a control and a case sample
Controls are as similar 'environmentally' as possible to cases, same sex ethnicity, socioeconomic back ground etc.
Look for common variants (SNPs) that are present much more significantly in the cases than the controls - if significantly more frequent in the cases then you have found an allele with an association
What kind of analysis is used to identify genes implicated in mendelian diseases?
Look for the pattern of inheritance in a family, look for an allele or patch of chromosome that exactly follows that inheritance pattern
Are genes with high magnitude of effect and low frequency in the population more likely to be implicated in mendelian or multifactorial disease and how are they likely to be identified?
Likely to be mendelian
Identified by linkage analysis
Are genes with a low magnitude of effect and high frequency in the population likely to be implicated in mendelian or multifactorial disease and how are the likely to be identified?
Why are genes with low magnitude of effect and low frequency in the population not analysed?
They have little clinical significance
What are SNPs?
Single nucleotide polymorphisms
Alleles with one base changed, present in more than 1% of the population
What is the difference between a mutation and a polymorphism?
Polymorphism is a mutation that is present in more than 1% of the population
What does linkage disequilibrium refer to and how does this affect association studies?
Refers to the fact that there will be some SNPs that have a high association with a disease causing SNP but arent actually disease causing themselves
This is because most disease causing mutations are descended from one or few ancestral chromosomes and over generations as that mutated allele is inherited, the alleles around it are inherited too
Means in association studies some of the SNPs with associations shown will not be disease causing themselves but are strongly associated with the disease causing allele