Genetics Flashcards
gene
determinants of a particular characteristic
- can be heterozygous or homozygous
allele
variant form of a gene
genotype
genetic constitution summing all of the alleles
phenotype
observed form of a character of an organism
Mendel’s Experiments
- proposed rules to predict types of progeny and proportions of each type knowing information about the parents
- single gene model with equal segregation of alleles
DNA during cell division
- meiosis separates homologous chromosomes
- sister chromatids separate and migrate to opposite poles (mitosis)
- meiosis gives cells with single versions of each allele
- each gamete has one version of an allele
Dihybrid Ratios
- Mendel looked at two genes segregating in the pea hybrids
- independent assortment of alleles shows each possible fertilisation event is independent of each other
Wild-type and mutant alleles
wild-type: more frequent allele
if there is no wild type allele the gene would’ve been polymorphic
Sex-linked inheritance
- females have homomorphic pair (X,X)
- males have heteromorphic pair (X,Y)
Sex linked traits more often found in males and are carried on the X chromosome
Lethal alleles
- disrupt 3:1 ratio
eg. agouti mice: - YY allele is lethal, but Yy is not
- therefore 2:1 ratio (Yy:yy) is produced indicating a lethal allele is present
Environmental influence on phenotypes
- Phenylketonuria (PKU) - rare recessive allele
homozygotes have severe mental retardation - Codes for Phenylalanine Hydroxylase
- Affected individuals can’t convert Phe to Tyr
- Phe accumulates in cerebrospinal fluid.
- Changing diet (environment) of PKU individuals at birth (to low protein) allows them to be virtually normal (wild type)
Departures from Mendelian Ratios
- if more than one gene affects the same characteristic, novel phenotypes and unusual ratios will appear
- this is still the Mendelian dihybrid ratio, but with differing phenotypes:
9 doubly dominant phenotype
3 dominant first recessive second gene
3 recessive first dominant second gene
1 doubly recessive
Genotype Masking
recessive epistasis: the expression of one gene pair is dependent on another gene pair
eg. laboradors
- recessive ee genotype (yellow) masks expression of any other genotypes (B)
Gene Linkage + Crossing Over
- genes on the same chromosome are usually inherited together
- causes differing allele ratios
- crossing over is the breaking and rejoining of homologous chromosomes in the same position to generate recombinants
Genetic Maps
- The phenomenon of recombination or genetic exchange allows for the construction of genetic maps
- Genes are placed on the map as a result of linkage to other genes whose position is already known
- The map distance is the unit of recombination - 1% of recombination frequency or 1cM
DNA based markers for genetic mapping
- Since there are so few genetic markers in humans, use DNA sequence variation to detect molecular alleles
- Forms the basis of the genetic map of the human genome
- This was a necessary pre-requisite to whole genome sequencing since the genetic markers acted as landmarks for the sequencing
Restriction Fragment Length Polymorphism
- digest DNA with restriction enzymes
- fragments separated by electrophoresis and visualised with Southern blotting
- hybridization with DNA probe determines lengths of complementary fragments
- RFLPs occur when the length of a detected fragment varies between individuals indicting non identical sequence homologues
Cystic Fibrosis Gene Cloning ***
- DNA based markers have allowed for the identification of disease genes such as the cystic fibrosis transmembrane conductance regulator (CFTR)
- Finding several closely linked markers eventually allowed the gene to be identified by positional cloning
- identification based on proximity to known markers
- presence of site: small fragment because of cut and vice versa
- used KM19 locus that was a restriction site and is very close to CFTR gene
Positional Cloning ***
Forms overlapping clones and identifies genes by its position in the genome
- take probe (identifies difference between 2 genotypes) and identify clone place of DNA by hybridizing to genomic libraries
- form overlapping clones to walk along genes
Linkage Disequilibrium
- nonrandom association between 2 loci
- groups of alleles of closely linked genes remain stick together = disequilibrium
- haplotype: tightly linked allele groups
- if you know the allele of one locus in a haplotype you can predict other alleles in this locus
Gene Association Studies
- compare SNPs of case studies against controls
- look for SNP alleles that associate with gene of interest
- variants will be more present in those with the trait
- this defines a region of the genome that may contain a candidate gene
- identifies associations between loci and traits
