Genetics of Complex Disease Flashcards
What are the 4 types of Genetics of Disease?
Single Gene Mutation
Multifactorial/Complex
Chromosomal
Enviromental
Describe what Single Gene Mutation is?
Rare, mutations in a gene to do with structural proteins and enzymes
Describe what Multifactorial is?
More than 1 Gene is affected, the Gene expression is on or off
Describe what Chromosomal changes are?
100’s of genes affected, gain or loss of a chromosome
Describe what Environmental factors mean?
Very common, could be viral/bacterial infections
What is the Definition of Multifactoral Inheritence?
Inheritance and expression of a phenotype determined by the action of multiple genes and multiple loci
What are the key features of Multifactoral Inheritance?
- Gene contributes to small amount of final phenotype
- Multiple genes not recessive/dominant
- multiple genes to segregate in Mendelian manner NOT PHENOTYPE
What are Monogenic Diseases?
Single strong high penetrate phenotype, rare and other genes affect phenotype severity
What are Polygenic diseases?
Very common, low penetrant phenotypes, not dominated by one gene, pedigrees comple and enviroment reduces pentrance
What does Pentrance mean?
Fraction of cases carrying a given gene that manifests in a specific phenotype
What would be the effect or a Fully Pentrant single gene?
No effect of other genes or enviroment
What would be the effect of low-pentrance?
Genes along with other genetic factors determine a persons susceptibility to disease
What would be the effect of Multifactorial?
Genetics determines susceptibility but has low penetrance e.g multiple sclerosis
What are the 2 Factors that cause any trait?
Genetics
Enviroment
What are some Examples of Polygenic complex disease?
Hypertension Obesity Diabetes Chrons Cancer Autism
Why study genetics of multifactorial disease?
Identify individual with increased risk of disease
Identify targets for better therapy
Untangle complex gene-enviro interactions
Why is Complex inheritance an underlying factor for most common human diseases?
Multifaceted interactions of genotypes at multiple loci
Environmental factors that trigger acceleate or worsen disease
What percentage of the population have complex disorders?
60
What is Polygenic Inheritance?
Traits quantified by measurement
More than 2 genes contributing to phenotype
Give an Example of Polygenic Inheritance?
Adult Male height
How is Adult Male height measured?
Median of Population
Bell curbe
Quantitive traits at 180 genetic loci
What Methods allow to study multifactorial traits?
Threshold Model
Recurrence Risk
Liability Threshold
Describe Threshold model?
Frequency of disorder of relatives compared to frequency of disorder with population
Describe Recurrence risk?
Estimates risk that disease will recur
Describe Liability threshold?
Measures disease state of indiv, when alleles push distrubtion towards threshold termed Risk/Susceptibility alleles
How do we know a complex disease has a genetic component?
Heritability - proportion of disease variation, defined as number between 0 and 1
What number = High genetic influence?
1
What number = NO genetic infulence?
0
What are monozygotic twins?
Identical - single fertilization
What are dizygotic twins?
Fraternal - independent fertilization events, share half there genes
What is Concordance?
Probability that twins will both have the disease if 1 has the disease
What type of Twins have a higher Concordance with diseases?
Monozygotic
How much Familial Risk is accounted in Familial Breast cancer?
< 30 %
What is Autism?
Great difficulty in communicating, forming relationships - strongly influenced by genetics
What is an Allele?
One of a number of alternative forms of the same gene
What is a Single Nucleotide Polymorphism (SNP) ?
DNA sequence variation that occurs when a single nucleotide in the genome sequence is altered at same genetic location between different chromosomes
Describe SNP?
Variation must occur in >1 % of the population, act as biological markers - help identify genes associated with disease
How can SNP’s be useful?
Used to track inheritance of diseases in families
What are SNP’s used as markers to map?
Haplotypes
What are Haplotypes?
Disease-linked genomic loci physically linked on a chromosome and segregate together
What is GWAS?
genome-wide association study
Describe Chromosomal disorders?
Usually de novo can be inherited
Thousands of genes involved
Multiple organs affected at multiple stages
What is an Aneuploidy?
Presence of an Abnormal number of chromosomes in a cell
What are the Sex chromosomes?
Triple X syndrome - 47 XXX
Klinefelter syndrom 47 XXY
XYY syndrome - 47 XYY
Turner Syndrome 45 X0
What are the Autosomal chromosomes?
Trisomy 21 - down syndrome
Trisomy 18 - edward syndrome
Trisomy 13 - Patau syndrome
What is DiGeorge syndrome?
Deletion of band 11.2 on long arm of chr 22 , 45 genes
What are some Symptons of DiGeorge syndrome?
Congenital cardiac defects, facial dysmorphia, T-cell
What is the Cause for T21 Down syndrome?
Mieotic non-disjunction
What is non-disjunction?
Failure of chromatids to seperate into 2 chromosomes
What is the Pedigree, Traits and Underlying cause for Mendelian?
Predictable inheritance pattern
Independent action of single gene
Mutation in this gene necessary for phenotype
What is the Pedigree, Traits and Underlying cause for Complex?
Familial clustering but not predictable inheritance pattern
Interactions between multiple genetic and enviro factors
Genetic variations increase susceptibility
