Risk calculations, test performance metrics, population genetics, and Bayesian analysis.
Chapters
Predictive values answer the clinically relevant question: given a test result, what is the probability that the patient actually has (or does not hav
Sensitivity and specificity describe the intrinsic performance of a diagnostic or screening test. They are properties of the test itself and do not ch
Bayesian analysis updates a prior probability (based on pedigree or population data) with new conditional information (test results, family history, u
Linkage analysis uses the coinheritance of genetic markers with a disease locus to track disease alleles through families. It relies on the principle
Autosomal dominant (AD) conditions require only one pathogenic variant for disease expression. Risk assessment must account for penetrance, variable e
Autosomal recessive (AR) risk assessment involves calculating the probability that an individual is a carrier or will have an affected child, based on
Xlinked risk assessment requires tracking the X chromosome through the pedigree. Males are hemizygous (one X), so a single pathogenic variant causes d
The binomial distribution calculates the probability of a specific number of successes (e.g., affected children) in a fixed number of independent tria
Probability rules are the building blocks for all genetic risk calculations. Before tackling Bayesian analysis or binomial problems, you need to be co
The HardyWeinberg principle states that allele and genotype frequencies in a population remain constant from generation to generation in the absence o
Mutationselection balance is the equilibrium state where the rate of new mutations introducing deleterious alleles into a population equals the rate a
Natural selection acts when genotypes differ in their reproductive success (fitness). Over generations it changes allele frequencies in predictable di
A founder effect occurs when a small subset of individuals establishes a new population, and that subset carries (by chance) allele frequencies that d
Genetic drift is the random change in allele frequency from generation to generation due to finite population size: a sampling effect. Gene flow, in c
Consanguinity is the mating of individuals with a recent common ancestor. It increases the probability that offspring will be homozygous by descent fo
Odds ratios (OR) and relative risk (RR) quantify the strength of association between an exposure (e.g., a genetic variant) and an outcome (e.g., disea
A genomewide association study (GWAS) scans the genome for common genetic variants (typically SNPs with minor allele frequency >1%) that are statistic
