Genetics term 2

Genetics term 2

1. Basic principles of inheritance

   • Definitions
     • Diploid- cell containing two complete sets of chromosomes
     • Haploid- cell containing a single set of unpaired chromosmomes
     • Locus- position of gene
     • allele- different forms of a gene
     • Genotype- sum of all the genetic information in a cell
     • phenotype- all the observable traits
     • homozygote- has two identical alleles for a gene
     • heterozygote- has two different alleles for a particular gene
   • Mednel's laws
     • 1- ALLELES SEGREGATE FROM ANOTHER AT GAMETE FORMATION (during meiosis alleles separate into gametes)
     • 2-DURING GAMETE FORMATION, ALLELES FROM DIFFERENT GENES SEGREGATE INDEPENDENTLY ***********
     • 3- RECESSIVE ALLELES WILL ALWAYS BE MASKED BY DOMINANT ALLELS
       • so heterozygote will have dominant phenotype. determine using a testcross. mate with known homozygote and use offspring ratio to determine genotype
   • exceptions to mendel's laws
     • 3rd law (dominance)
       • incomplete dominance -phenotype of heterozygote distinct/ often intermediate between phenotype of the two homozygotes
       • co-dominance- both alleles contribute to the phenotype AND THE EFFECTS OF BOTH ALLELES ARE SEEN TO THEIR FULL EXTENT
     • epistasis- phenotype caused by one gene is influenced by one or more other genes
       • e.g. bald gene and hair gene, if the bald allele is present the hair colour will not be expressed in phenotype (bald epistatic to hair colour)
     • sex-linkage- most genes on x have no homologue on y. males are hemizygous for genes on X. x- linked recessive inhertience, males only require one recessive allele to express in the phenotype
     • Genetic linkage- BREAKS 2ND LAW. genes on the same piece of DNA are physically linked, not always able to segregate independently
       • on same chromosme= same linkage group- often stay together
         • increase in parental genotype decrease in recombinant genotype

2. evolution and speciation (genetic diversity)

   • chromosome structure- p arm is the short arm, q arm is the long arm. centromere where kinetocore fibres attach
     • alternative splicing- means more than one type of protein can be produced by the same gene 
   • repetitive DNA
     • Tandem Repeats- repetative sequences in telomere DNA to protects the ends of chromosomes- shorten with age
     • interspersed DNA- intermingle with other sequences. transposable elements or derived from transposable elements. can affect, copy or move genes
     • regulatory sequences- enhancers, silencers or insulators
       • cis vs trans consrved or non conserved
   • Genetic mapping
     • genetic marker= sequence with known location on chromosme
     • Genetic map= representation of markers on a chromosome in linear order distances expressed as % recombination
       • requires really large population if close together it's impossible to resolve since there will be little or no recombination
     • physical map- physical position of markers on chromosome
       • cytogenic map- position of a known DNA fragment by in situ hybridisation (FISH)
       • genome sequencing another form of physical map

3. Population genetics

   • the environment and genotype produce phenotype, extent to which genetics contribute to a trait is the heritability
   • h squared is the genetic varience as a proportion of phenotypic varience
   • EBV= estimated breeding value can estimate for all traits. calculated using BLUP (best linear unbiased prediction)
     • combines performance information and pedigree information
       • allows fair comparison of animals of different ages
     • selection indexes- allow to select for more than one trait by combining EBV
   • Genomic selection- genotype proven bull with reliable ebv, find markers with effect on the ebv and calculate the marker effect for each trait. genotype selection candidates and calculate GEBV using marker effects from reference sires- select for animals with highest GEBV

4. polymorphisms and mutations

   • polymorpism= genetic varient present in more than 1% of the population- generally non pathogenic
   • mutation- event that perm changes DNA sequence
     • can be point mutation or frame shift 
   • missense mutations- non-synonymous mutation causes one amino acid to be replaced with another
   • nonsense mutations- create stop codon too early also non-synoymous
   • Frameshift- entire reading frame out of sequence, often leads to a premature termination codon PTC
     • NMD- nonsense mediated decay. a normal stop codon is always downstream of the last exon junction complex. if the mutation produces PTC before final EJC NMD is activated and prevents the protein being produced
       • degrades mRNA

5. Diagnostic DNA

   • Karyotyping- number of chromosomes and gross changes in structure- chromosomes must be in metaphase
     • high res- array comparative genomic hybridisation, sample and reference labelled then hybridised. added to chip spotted with bits of each chromosme, then scanned by a computer which quantifies differences in chromsomes
   • DNA profile (VNTR)- variable number tandem repeats. similar in related individuals. break samples into fragments using restriction enzymes then doing a gel eleoctrophoresis and southern blot. incubate with probe which binds to VNTRs and image on photographic film
   • Restriction fragment length polymorphisms- uses restriction enzymes if the mutation falls within the recognition site. incubate PCR product with enzyme, normal incubation will produce two fragments where the enzyme has cut. a mutation in the recognition site means enzyme will not cut so only one fragment produced
   • DNA sequencing- identify variations using sanger method- limited to 500bp and error prone, in future sequencing technology will be more reliable and cheaper