Terminology Flashcards
Locus
A unique chromosomal location
Allele
different variants of the same coding sequence (locus)
Homozygous
identical maternal and paternal alleles
Heterozygous
non-identical maternal and paternal alleles
Hemizygous
only having inherited one allele
Genotype
genetic characteristics/ combination of alleles in an organism
Phenotype
observed genetic characteristics/traits shown by the individual
mutation
process that gives rise to chages in base sequences or the outcome i.e. the altered sequence
substitution
the change of one nucleotide to another
deletion
one or more nucleotides are deleted (can also occur with larger chromosome fragments)
insertion
on or more nucleotides are inserted (not a copy of the ones around)
(can occur with both small and larger segments)
duplication
a copy of the sequence directly close by is inserted (can occur with both small and larger segments)
inversion
original nucleotide sequence is reversed and flipped 180 degrees (can occur with both small and larger segments)
conversion
sequence copied from another site in the genome replacing the original sequence
balanced structural variation
the DNA variant has the same content but some of it is located somewhere else in the genome
translocation
two different DNA molecules (chromosomes) receive a double strand break and exchange fragments without any change in content
Indel
collective name for insertion/deletion
unbalanced structural variation
DNA variants that differ in DNA content compared to the reference
CNV
copy number variation eg. large indels or tandem duplications
De novo mutation
a new variant apparent in neither of the biological parents
Genetic mosaicism
a state which an individual has 2 or more genetically different sets of cells in his/her body occurs eg if mutations occurs early during embryonic development
SNP
single nucleotide polymorphism. A DNA variant that only spans one base pair, Needs to be present in at least 1% of the population
Neutral variation
variation which has little to no effect on the phenotype
Population genetics
The science of allele frequencies and how they differ between populations and subpopulations
Haplotype
combination of alleles at the same chromosomal segment
gene pool
all alleles at a given locus across a population
The Hardy Weinberg Equation
a mathematical equation that can be used to calculate the genetic variation of a population in equilibrium. p^2+2pq+q^2=1
p+q=1
Linkage Disequilibrium
the tendency of some alleles to be transmitted together more or less often than expected by chance alone. usually caused by close proximity of genes on the same chromosome
Haplotype blocks
Blocks of the genome that are created by correlated SNPs inherited together
genetic drift
changes in allele frequencies due to chance
Heterozygosity measure (Nei’s statistics)
probability that two alleles at a locus drawn at random from a population will be different from each other
population mutation parameter Ꝋ
the diversity per nucleotide that is expected due to the balance between mutation creating new alleles and drift to fixation eliminating them
Diversity: the bottle neck effect
a drastic reduction of effective population size, leaving only a lower random set of alleles
Founder effect/event
when a small number of individuals form a new population with their set of alleles
negative selection or purifying selection
the selective removal of alleles that are deleterious
dN/dS
the ratio of nonsynonymous to synonymous substitutions
positive selection (darwinian selection)
promotes frequency of advantagous DNA variants
Fst (st subscripted)
a measure of how different two (sub)populations are by considering how much heterozygosity would be gained if the two were a single random-mating population (F= 0 –> identical populations F=1 compleate separation)
genealogical ancestry
individuals who would feature in your genealogy if you were able to trace it all the way back
Genetic ancestry
Individuals from whom you inherit significant parts of your genome
coefficent of inbreeding
the probability that an individual recive two alleles at a given locus that are identical by decent
coefficent of relationship
the proportion of alleles two individuals share that are identical by decent
Identical by state (IBS)
the same DNA sequence but might not be from the same descent
Identical by descent (IBD)
the same DNA sequence (alleles) that are due to same ancestry
effective population size
proxy of the number of individuals in a population that contribute their genes to the next generation
Mutation-drift equilibrium
variation is gained by mutation at the same rate as it is lost by drift and selection (–> the effective population size stays the same)
autosome
A chromosome which is not a sex chromosome
p-arm
the short (petite) arm of the chromosome
q-arm
the large arm of the chromosome
centromere
part of the chromosome which separates the p and the q arm
telomere
repetitive DNA sequences at the end of the chromosomes which protects them from damage
zygote
a fertilized egg
karyotype
a photomicrograph of the full set of chromosomes in metaphase from a single cell nucleus arranged in pairs in descending order of size
Aneuploidies
the chromosomal constitution of cells which deviate from the normal by addition or subtraction of chromosomes
Trisomy
three copies of a chromosome
monosomy
one copy of a chromosome
non-disjunction
that a pair of chromosomes has failed to separate or segregate at anaphase –> both chromosomes pass to the same dauther cell
sub-microscopic structural rearrangements
small deletions, tandem duplications, inversions, insertions etc. (but still on chromosome level?)
haploinsufficency
a genetic variation that results in reduced gene dosage
Contigous gene syndromes
Disorders caused by deletion of multiple gene loci that are adjacent to one another. Contiguous gene syndromes are characterized by multiple, apparently unrelated, clinical features caused by deletion of the multiple adjacent genes
congenital abnormalities
structural or functional abnormalities that occur during intrauterine life
gene dosage
the number of copies of a single gene within a genome
copy number variation (CNV)
phenomenon which sections of the genome are repeated and the number of repeats in the genome varies between individuals
recombination
the process by which genetic material is exchanged between the two homologous chromosomes
meiosis
cell divisions where haploid germ cells are generated
gene
region encoding a protein or an RNA molecule
homologues
the pair of two corresponding chromosomes or genes
Chromatide
one of the homologous chromosomes
Haplotype
combination of linked alleles on the same homologue
SNV
single nucleotide variant. A DNA variant that only spans one base pair. unlike SNP does not have to be present in a specific frequency in the population
mutation
rare allele. Under 1% of the population has it, often associated with disease
polymorphism
common allele (above 1% in the population) may be associated with increased disease RISK
penetrance
percentage of individuals with a specific genotype showing the phenotype
dominant
alleles which influence the phenotype both in homozygous and heterozygous state
recessive
alleles that only influence the phenotype in the homozygous state
Consanguineous parents
parents which are related
the two hit model/hypothesis
The hypothesis that most tumor suppressor genes require both alleles to be inactivated eg. one inherited mutation and one somatic mutation
genetic heterogeneity
different genes may if mutated cause the same phenotype
allelic heterogeneity
different variants in a specific gene may cause variable phenotypes
Lyonisation
x-chromosome inactivation
Imprinting
the variable phenotypic expression of a gene depending on whether it is of paternal or maternal origin which is a function of the DNA methylation pattern. Imprinted regions are observed to be more methylated and less transcriptionally active
mendelian disease
monogenetic disease. difference in a single gene
STR markers
short tandem repeat markers (microsatellites) eg used in forensics
multiplex PCR
methods for using more than one primer set in a polymerase chain reaction to amplify more than one segment of the target DNA sequence in a single reaction
miniSTRS
reduced size STR amplicons which are created by moving the forward and reverse primer in close to the STR repeat region
orthologous (genes)
genes in different species that derive from a common ancestral gene (the splitting of lineages)
paralougous (genes)
genes that are homologous due to an ancestral gene duplication event
microsatellites
non-coding tandem repeats of two to six nucleotides
pseudogene
genes bearing close resemblance to known genes at different loci but rendered non-functional by additions or deletions in structure that prevent normal transcription or translation
retropseudogene/ processed pseudogenes
pseudogenes which lacks introns and contain a poly-A segment near the downstream end
retrotransposition
insertion of DNA sequences mediated by an RNA intermediate
alternative splicing
a process whereby multiple RNA transcripts are generated from a single gene –> alternative forms of mature messenger RNA
ELSI
Ethical Legal Social Implications of human genome research
ENCODE
the ENCyclopeadia Of DNA Elements - a project which aims to identify all functional elements in the human genome
GWAS
Genome Wide Association Study. A study based on analysis comparing allele frequency of all available polymorphic markers (DNA markers/mutations/SNPs) in unrelated patients with a specific condition and those of healthy controls to identify markers associated with a specific condition
HapMap project
project aimed to develop a haplotype map of the human genome describing the common patterns of human genetic variation
VNTRs/SSRs
variable number tandem repeats/ single sequence repeats. Tandem repeats that vary greatly in number among individuals
minisatellite
non-coding tandem repeats of 10-100 nucleotides
copy number neutral loss of heterozygousity
a phenomenon whereby one of two homolougous chromosomal regions is lost but various mechanisms have ensured the presence of two identical copies of such region in the genome eg. you get 2 alleles from your mother but non from your father or by mitotic recombination
epigenetics
the study of heritable changes in gene function that cannot be explained by changes in DNA sequence
pharmaco-genomics
the science of understanding the correlation between the individual patients genetic make-up and their response to drugs
heritability
the degree of the phenotypic variation (in a population) that is estimated to be caused by genetic differences
oncogene
a gene in which gain of function alterations lead to neoplastic cell transformation
tumor suppressor gene
genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check
complex disease
difference in multiple genes in addition to environment
genetic marker
a DNA sequence with a known physical location on a chromosome (e.g. SNVs and microsatellites)
genetic mapping
the process of establishing the locations of loci on the chromosomes
genetic distance
the distance between two loci based on recombination fraction. The genetic length over which one crossover occurs in 1% of meioses. Expressed in cM (centi-Morgan)
linkage
the tendency of genes or other DNA sequences at a specific loci to be inherited together as a consequence of their physical proximity on a single chromosome
linkage analysis
mathematical model of the extent to which a given marker tends to be co-transmitted with a disease through families. Can result in mapping a disease to a specific chromosome region
LOD score
a statistical measure of the likelihood of obtaining the test data if the two loci are linked to the likelihood of observing the same data purely by change (likelihood of linkage/likelihood that the loci are unlinked)
Autozygosity
when you are homozygous due to the fact that your maternal and paternal chromosome are derived from the same common ancestor
sensitivity
measure of how often a test correctly generates a positive result for people who have the condition (e.g. how rare are false negatives)
specificity
measure of the ability of a test to correctly generate a negative result for people who don’t have the condition (e.g. how rare are false positives)
Precision/accuracy
How reproducible or correct a test is
utilitarianism
an ethical principle that says that actions (good/bad) should be evaluated based on their consequences
duty ethics
an ethical principle that judges the intention of an action rather than the consequence/ some actions are prohibited regardless of the consequences
virtue ethics
an ethical principle that judges the character of a person rather than isolated actions i.e. an action is right if it is the kind of action that a virtuous person would do
ccffDNA
Circulating Cell Free Fetal DNA
missense mutation
a point mutation leading to an amino acid substitution
nonsense mutation
a point mutation leading to a premature stop codon in turn leading to a truncated protein
splicing mutation
a mutation that occur at the boundary of an exon and an intron which disrupts the RNA splicing
frame-shift mutation
a small deletion or addition (duplication) of nucleotides which causes a shift in the reading frame of the RNA leading to many incorrect amino acids in the protein
trinucleotide repeat expansions
increased number of a particular series of nucleotides eg. CAG leading to disease
(genetic) anticipation
The tendency that a disease appears to be more severe in later generations
