Allred 2 Flashcards
Phenotype
The observable property of an organism; a trait such as height, weight, medical condition, etc.
Genotype
The DNA sequence at a specific, defined location; not necessarily observable; can be expressed in a variety of ways
Allele
A DNA sequence at a specific chromosome; the genotype is made up of alleles, one allele per chromosome; all DNA sequences (not just genes) are alleles
Homozygous
Two identical alleles at the same locus
Heterozygous
Different alleles at the same locus
Dominant trait
A single copy of the gene (allele) is sufficient to express phenotype
Recessive trait
Two copies of the gene (allele) are necessary to express phenotype
Codominant trait
Both alleles are expressed as observable phenotypes
Blood Type A
UDP-N-acetylgalactose
Blood Type B
UDP-Galactose
Blood Type O
No additional sugar attachment
Locus
A specific location on the chromosome (plural: loci)
ABO Blood Group
Multiple alleles in the population at the ABO locus; there are multiple combinations of alleles to create multiple genotypes/phenotypes
Why are mouse models used in genetic studies?
Answers questions that ask if two genetic loci are on the same chromosome
Chiasma
INSERT
Silent mutation
A change in base pairs that does not lead to a change in amino acid sequence; synonymous change
Nonsense mutaion
Premature termination
Missense termination
A change in base pairs that leads to a change in amino acid sequence; nonsynonymous change
Frameshift mutation
Addition or deletion in nucleotide sequence
Autosomal Dominant Disorder
A genetic disorder that requires one copy of the mutated gene to express the disease
Can be caused by new mutation, or due to penetrance and expression variability
Penetrance
The likelihood of the presence of a disease when the mutation is present
Variability of expression
The disease has a wide range of phenotypic expression
Autosomal Recessive Disorder
A genetic disorder that requires two copies of the mutated gene to express the disease
Early onset of disease
Fully penetrant
Found with genes that encode for enzymes
X linked disorders
Expressed in males; females with the gene are obligate carriers; all daughters of affected fathers are carriers
Mitochondrial disorders
Nonmendalean
No transmission from affected males
Affected females transmit disease to all of their offspring
Disease involve oxidative phosphorylation defects
Gene heterogeneity
more than one gene can contribute to phenotype
Gene-Gene interaction
both genes combined have an effect
Gene-environment interaction
Gene suseptibility only observed in the presence of specific environmental triggers
Phenocopies
The same phenotype caused by environmental factors only
Epigenetics
Modification of histones or DNA sequence by environmental factors
Types of polymorphisms
Microsatellites (SSR)
Single Nucleotide Polymorphisms (SNP)
Single nucleotide polymorphism
Single base changes
Naturally occuring variants
Most do not account for phenotypic variability, no “normal” or “wild-type” allele
Used mostly for candidate gene and genome-wide association studies
May be slight changes for gene functioni or expression levels
Can be in the intron/exon
How can a SNP affect susceptibility of a complex disease?
Many complex diseases occur later in life
SNPs cause slight changes in gene expression levels or function that take time to lead the clinical phenotype
Initially the body will compensate for SNP effects, but will eventually lose the ability to do so
Where does the SNP effect?
Exons: Protein structure or function Promoter/Enhancer: Expression level Introns: splicing or expression level 5' UTR: ribosome binding, protein level 3' UTR: Transcript stability
Linkage Disequilibrium (LD)
The non-random association of alleles at two or more loci
LD Differs by genomic region
LD Differs by genetic ancestry
Steps for Disease Gene Identification
Is there a genetic component Research subject ascertainment Measurement of phenotype Molecular/Analytical analysis Functional analysis
Genetic component factors
Twin concordance
Familial aggregaion
Genetic subject ascertainment
Sib-pair
Families
Case-control
GWAS
Genome-wide association study
Scan the genome using > 1m SNP to search for variants that differ in frequency between cases and controls; identifies common genetic variants with a weak influence on the phenotype
