Lect 1: Genetics Refresher (3 Genetic Disorder Models (Mendelian: 1-4%…
Lect 1: Genetics Refresher
3 Genetic Disorder Models
Known pattern of inheritance -> autosomal recessive, autosomal dominant, sex-linked disease (x-linked recessive, X-linked dominant, y linked)
Genetic mutations but x cause trait as incomplete penetrance
E.g. -> Haemachromatosis (Fe overload -> autosomal dominant illness) -> major gene,HFE, on chromosome 6 -> 2 gene copies -> ill but clinically less likely in women -> Unknown why!
Although having genotype at 1 locus -> phenotype x always expressed -> late onset illness
Cystic fibrosis -> Autosomal recessive
Huntington Disease -> Autosomal dominant
Mendel's studies of inheritance patterns in pea plants -> current understanding of single-gene diseases in humans.
Mendelian/ monogenic diseases -> cause: mutations in one gene & sometimes run in families.
Pedigree analyses of large families with many affected individuals -> det if disease-associated gene loci -> autosome/sex chromosome + whether the disease phenotype -> dominant/recessive
Complex disease: 70-95% of human disease dep on cancer inclusion
Chromosomal disease: <1%;rare
causes visible chromosome alteration / produced via specifically chromosomal mechanism
Constitutional (inherited) abnormalities -> all cells
Either numeric or structural
Triploid (3 copies) -> 2 sperm fertilising an egg
Tetraploid (4 copies of whole genome)
Aneuolidy -> extra copy of >1 chromosomes -> x compatible w life
Trisomy: Down’s Syndrome: 3 copies of Ch. 21
Monosomy: 1 chromosome missing -> Turner’s syndrome
proportion of individuals carrying a particular variant/ allele -> also express an associated trait
penetrance of disease-causing mutation -> proportion of individuals with mutation who exhibit clinical symptoms.
complete penetrance -> disease-causing mutation have clinical symptoms
Incomplete penetrance -> some x express trait even though carry mutant allele.
E.g. autosomal dominant condition showing incomplete penetrance -> familial breast cancer -> BRCA1 gene mutation -> 80% risk of breast -> penetrance 80%
Highly penetrant allele -> trait produced always present
Low penetrant allele -> occasionally produce trait; difficult to distinguish environmental from genetic factors.
Genome -> complete set of genetic info in cell & includes 23 pairs of chromosome & mtDNA
Human genome -> >20 00 genes -> each being single inheritance unit
location of gene on chromosome -> locus -> genetic variation here -> allelic variation -> diff forms known as alleles
SNP -> change in single bp (point mutation)
most common type of genetic change in humans (cause 90% of genome variations)
As genes inherited on chromosomes -> genetic variations inherited as haplotypes
Haplotypes change from 1 gen to another -> recombination during crossover (meiosis)
Phenomena -> alleles on same chromosome -> transmitted tgt over gen within popn & such alleles found tgt more frequently than expected
non random segregation of alleles
Due to physical proximity of alleles & low rate of segregation at meiosis
Tool for understanding GWAS/GWLS
Haplotype: allele grps at diff loci -> inherited as a unit