ST2 notes Flashcards
allelic heterogeneity
different mutations of the same gene
locus heterogeneity
same mutation in different genes
Bardet-Biedl syndrome (BBS)
15 loci are responsible for cilia functions making it a pleiotropic disorder as many different body systems are impaired
shows locus heterogeneity
pleiotropy
one genes influences two or more seemingly unrelated phenotypic traits
Sensorineural deafness
same mutation in 28 different genes
autosomal recessive but two different parents can have a normal child if they have different disease genes
normal child will be a double heterozygous as they will have two different mutant genes
shows locus heterogeneity
genomic imprinting
offspring’s gene expression is parent-specific due to inactivation of the opposite parent’s allele
caused by DNA methylation that suppresses transcription resulting in alterations in gene expression
imprinted gene
methylated and inactive in somatic cells
maternal imprinting
maternally derived allele inactivated
paternal imprinting
paternally derived allele inactivated
Prader-Willi syndrome
maternal imprinting
deletion of paternal chromosome 15q11
Angelman syndrome
paternal imprinting
deletion of maternal chromosome 15q11
uniparental disomy
two copies of a chromosome are inherited from one parent and no copies from the other parent
caused by non-disjunction followed by loss of genetic information
heterodisomy
meiosis I non-disjunction
both homologs from one parent
isodisomy
meiosis II non-disjunction
one chromosome is duplicated
modifier gene
gene that alters the expression of a human gene at another locus that in turn causes a genetic disease
epistasis
effect of a gene mutation is dependent on the presence or absence of mutations in one or more other genes (modifier genes)
linkage analysis
family-based
makes use of pedigrees for mapping of monogenetic diseases
association analysis
population-based mapping comparing the frequencies of alleles in affected individuals to unaffected controls for complex diseases
haplotype
series of alleles at linked loci that are co-inherited on a single chromosome
recombination frequency (theta)
estimate of genetic distance
theta = 0.5
NR = R
loci very far apart
theta = 0
only NR
loci very close together
theta < 0.5
NR>R
in-between
LOD score (Z)
likelihood ratio / odds ratio
Z > or equal to 1
suggests linkage
Z > or equal to 3
strong evidence of linkage
Z < 1
suggests linkage less likely
Z < -2
significant evidence against linkage
exome
all the exons in all of the genes in an individual’s body
complex/multifactorial diseases
caused by many different genetic factors - polygenic
influenced by environmental and chance factors
disease manifests once certain threshold is reached
polygenic
inheritance and expression of a phenotype is determined by many different genes at different loci
continuous/quantitative traits
normal phenotypic characteristics that everyone has but with differing degrees
can be measured - height, blood pressure
discontinuous/dichotomous/qualitative traits
disease is either present or absent
congenital disease or diseases that develop later in adult life
predisposition is inherited - relatives share more susceptibility genes and environmental factors
empiric risk
chance that a disease will occur or reoccur in a family
higher risk for more closely related individuals
heritability
indicates the importance of genetic factors compared to environmental factors
familial aggregation
affected individuals cluster in families
indicates genetic component - families have predisposition for qualitative diseases because of shared alleles
relative risk (lambda)
measures familial aggregation
lambda = prevalence of disease in relative of affected person/prevalence of disease in general population
larger lambda = greater familial aggregation
lambda = 1 - recurrence risk for relatives of affected individual is the same for any other individual in the general population
common disease-common variant hypothesis
disease risk in specific individuals is due to aggregation of common variants
common disease-rare variant hypothesis
rare variants are expected to be more deleterious and high penetrant
protective factors/variants
reduce the risk for common disease
protective factors for one disease can be a susceptibility factor for another disease
gene therapy
genetic alteration of the cells of a patient with a genetic disorder to achieve a therapeutic effect
gene augmentation
replaces a missing gene product by inserting a normal gene into a somatic cell
best for LOF mutations
gene silencing
targets pathogens in infectious diseases
silences active oncogenes
silences GOF mutant alleles in inherited diseases
in vivo
cells are modified within the patient’s body
difficult to monitor success
ex vivo
cells are removed from patient, genetically modified in cell culture, selected, multiplied and returned to patient
cells can be analyzed in depth before treating patient
non-viral delivery
synthetic vesicles known as liposomes form spontaneously when certain lipids are mixed in aqueous solution
lipid coat allows DNA to survive in vivo, it binds to cells and allows DNA to enter
can accept large DNA inserts
does not elicit immune response
efficiency of transport low
malignant neoplasia/cancer
consequence of genetic damage whose cumulative effect results in unrestrained cell growth, tissue invasion, and metastasis
sarcoma
mesenchymal tissue - fat, bone, muscle
carcinoma and adenocarcinoma
epithelial tissue
leukemia and lymphoma
blood forming tissue
pronto-oncogenes
components of signaling pathways that regulate cell proliferation and differentiation
tumor suppressor genes
block uncontrolled cell proliferation
participate in pathways that regulate the cell cycle
regulate upstream growth signaling pathways
may induce apoptosis
gatekeepers
classical tumor suppressor
central role in regulating cell proliferation by regulating cell cycle and growth
mutations lead directly to tumor development
