Introduction/creativity Flashcards
Constituents and size of the human genome
20,000 genes. 3x10^9 base pairs. extragenic DNA makes up roughly 70% of our genome and contains spacer DNA, control regions, repetitive sequences all with a largely unknown function.
Assumptions of HWE
- The population is infinitely large and the effects or random genetic drift are negligible.
- Mating is random with respect to genotypes (no consanguinity or assortative mating
- No new mutations introduce variability into the population
- Natural selection does not affect genotype frequencies
Factors that distort HWE
Founder effect, population bottleneck, non-random mating and consanguinity
Consequences of mutations on natural selection
Deleterious recessive traits are maintained in the population through heterozygous carriers
Genetic Drift
the change in frequency of an allele in a population due to random sampling
Founder Effect
part of a population is isolated for some reason or another, but one member of the population carries a deleterious allele leading to a higher frequency in the resulting population. ex. AJ’s and the Chmeilnicki massacre resulting in a small number of surviving jews (consider the repeated bottleneck of jewish people throughout history and that they remain a tight community)
Non-random mating
Geographic, cultural and social structures limit random mating, we tend to marry people similar to ourselves, 1/3 of marriages occur between people born less than 10 miles from one another. This is a major factor in changing human allele frequencies.
Complicating factors of reading a pedigree
- non-penetrance
- new mutations
- adult onset condition
- consanguinity
- interaction
- sex limited/sex influenced
- germline mosaicism
- anticipation
- heterogeneity
- pleiotropy
Characteristics of a complex polygenic trait
large numbers of isolated cases
increased risk to relatives
risk to relatives declines with decreasing kinship to proband
no recognizable pattern of inheritance
conditions that foster creativity
persistence and imagination, go outside the box, be open minded, create a safe environment, don;t procrastinate, be practical, talk to people about it etc.
Garrod’s view of disease and inborn errors of metabolism
Conceptual: what are diseases and why do they exist? Prevention becomes the primary focus. Approached on population level, but the individuals particular variation is emphasized.
Osler’s view
There should be no teaching without the patient. Books and lectures are seen as tools. The emphasis is fully on the disease, the patient is seen as a battleground. Treatment and management are the focus.
Current medical thought on disease
based in biology. Susceptibility, accumulating effects of genes and experiences becomes a disease that depends on the specificity of the genes and experiences as well as on the individual.
Genomic medicine
The use of genotypic analysis to enhance the quality of medical care, including pre-symptomatic identification of disease susceptibility, preventative intervention, selection of pharmocotherapy and individual design of medical care based on genotype.
Mendelian phenotypes and the human lifespan
Most mendelian phenotypes express early in life.
recessive traits tend to be more sever than dominant.
dominant tend to be expressed later in life (after reproduction, the only way this allele could survive natural selection).
modifier genes in mendelian disorders
Extensive variation is due to allelic heterogeneity, environmental and stochastic factors. Genotypes at other loci can also influence disorders.
Environmental factors in mendelian disorders
Major genes, modifiers, age, sex, parental effects, ethnic group, cognition, behavioral attributes, geography, time, climate, education, occupation, diet, habits, SES and disease.
