MED GEN EX 2

Admixture

the mixing of two or more previously isolated populations that had diverged in genotype frequencies, which tend to increase genetic variability in the next generations

Founder effect

when individuals leave an established population, and find a new group of people, typically only carry a subset of the variation in the source population and some alleles have altered frequencies

Linkage disequilibrium (complete/partial)

nonrandom association of linked genotypes on a chromosome due to the history of new mutations and the time taken for recombination to generate new haplotypes

Measured as correlation of genotype frequencies

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association of two linked alleles more frequently than would be expected by chance

Haplotype

multilocus genotype on a single chromosome

Purifying selection

natural selection that tends to remove deleterious alleles from gene pool

ensures that deleterious mutations are generally at low frequencies

Adaptation

evolutionary process where a species becomes more suited to the ecological and biogeographic niche it occupies as a result of natural selection favoring certain genotypes

Genetic Drift

process where isolated pops tend to diverge in allele frequencies

Aneuploidy

one or more chromosomes in a cell have a different number of copies than expected (usually diploid)

aCGH

array comparative genomic hybridization

method for detection of duplications or deletions of DNA regions by competitive hybridization of fluorescently labelled control and test DNA to a microarray of known, mapped sequences

Association

nonrandom combination of two or more structural defects that are not due to a single localised defect of embryogenesis

Balanced vs. Unbalanced aberration

any abnormality of a chromosome number or structure visible under a microscope

Causal relationship

Chromosome painting (forward/reverse)

forward: normal chromosome paints abnormal karyotype (normal → abnormal)

reverse: derivative chromosome used as probe (abnormal → normal)

Common disease-common variant model

model of genetic architecture of disease that postulates that a small number of relatively large effect common variants are responsible for cases of common diseases

Compound heterozygote

individual is heterozygous for two different mutations, one on each chromosome inherited from either parent

two different mutations at the same gene or two different mutations in the same pathway

Cross over

exchange of genetic material between homologous chromosomes during meiosis

De novo mutation

spontaneously occurring genetic alteration that is present in offspring, but not in parents

Dicentric

abnormal chromosome with two centromeres

Epigenome

chemical compounds that mark the genome

Expressivity

severity of the phenotype that is observed in individuals that have a disease/condition attributed to a large-effect scale

Flow karyotyping

histogram of chromosome DNA measurements generated by a fluorescence-activated cell sorter

Fluorescent in situ hybridization (FISH)

hybridization using a probe to bind to specific regions of chromosomes

Gene expression profiling

measuring abundance of all the transcripts that are found in a tissue in an individual

microarray analysis and RNA-sequencing are the most common methods

Genetic architecture

how multilocus genotypes maps onto phenotypes

Genotype Relative Risk (GRR)

risk that a person with a specific genotype has of contracting a disease, relative to the risk in the rest of the population

GWAS

studies designed to take an unbiased approach to discovering genes that contribute to disease risk of phenotypic variation by measuring hundreds of thousands of people

Illumina Sequencing

Imputation

process of inferring the most likely genotypes at polymorphisms that were not directly measured on a genotyping array using the known pattern of linkage disequilibrium in the pop in the vicinity of the region being imputed

Induced pluripotent stem cell (iPS)

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Infinitesimal model

model of genetic architecture of complex traits that posits that avg genetic effects are on avg very small, and therefore it takes several thousand polymorphisms to account for all of the genetic variance for a trait

most polymorphisms assumed to be common

Pericentric vs Paracentric Inversions

pericentric includes chromosome

paracentric does not include chromosome

Isochromosome

abnormal chromosome that loses an arm and has two identical copies of the other arm

Law of Independent Assortment

alleles of two genes assort independently into gametes

Linkage Analysis (Pedigree Mapping)

identifying regions of the genome that contain genetic risk factors for a disease by tracing the frequency of genetic markers in large pedigrees

alleles that segregate with the disease are said to be linked to a causal gene

Linkage phase

Logarithm of the odds (LOD)

logarithm of odds score for likelihood of two loci being within a measurable distance of one another

Manhattan plot

represent significance and association between SNPs and phenotype

Multiplex Ligation Dependent PCR (MLPA)

method of testing for CNV

PacBio SMRT sequencing

light only excites molecules next to glass, DNA pol next to glass, see pulses in fluorescence when a phosphodiester bond is made

Phasing

Polymorphism

nucleotide sites that have two or more alleles at a detectable frequency in a population

Population structure

existence of allele frequency differences that define sub-populations as founder effects, genetic drift, migration, and natural selection have caused groups of people to diverge genetically

QF-PCR

RAME

Rare allele of major effect

genetic variants that tend to be associated with larger genetic risk than common variants but are found in fewer individuals

Recombination

two homologous duplex DNA molecules exchange information by crossing over

Ring chromosome

Syntenic

loci on the same chromosome

Translocations

transfer of chromosomal material between chromosomes

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Reciprocal

Robertsonian

Insertional

Alpha fetoprotein (AFP)

Amniocentesis

Bayes' Theorem (Bayesian analysis)

Blastomere biopsy

cfDNA

Cherry red spots

Chorionic Villus Sampling (CVS)

Coefficient of inbreeding

Coefficient of relationship

Creatin phosphokinase (CPK)

Dating ultrasound

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Diagnostic test

Empiric risk

Gastroschisis

False positive/negative

Human Chorionic Gonadotropin (hCG)

Inhibin A (DIA)

Negative predictive value

Neural tube defect (NTD)

Newborn/neonatal screening

Noninvasive prenatal testing (NIPT)

Nuchal translucency

Omphalocele

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Polar body biopsy

Polygenic risk score

Positive predictive value

Pregnancy-associated plasma protein A (PAPP-A)

Preimplantation Genetic Diagnosis (PGD)

Prevalence

Quad screen

Recurrence risk

Screening test

Sensitivity

Specificity

Triple test

Trophectoderm biopsy

True negative/positive

uE3

Biologics

Biomarker

Cell-based therapy

CRISPR

Drug repurposing

Endotype

Enzyme replacement therapy

Epidemiology

Gene therapy

Genome editing

gRNA

IPS cells

Mendelian randomization

Pharmacodynamics