genetic counselling and linkage Flashcards
preimplantation test and prenatal test
- select disease free embryos for implantation
- detect potential genetic disease in foetus
screening test and pre-symptomatic test
- population-based test, providing a personalised risk assessment
- individual with no symptoms but has family history
carrier test and diagnostic test
- detects genetic variant which increases likelihood offspring will have a disease
- confirm in symptomatic patient a suspected diagnosis
societal implications of genetic counselling
- availability
- cost
- education to public
- privacy laws
research merit and integrity
potential benefit, well designed, follows principles of research conduct
justice
fair recruitment, and distribution and access of benefits
beneficence
likely benefit must outweigh the harm
non-maleficence = avoid doing harm
respect
autonomy of participants
respect privacy, confidentiality and cultural beliefs
what is genetic counselling
- interpretation of family and medical history
- education about inheritance, testing, management, prevention
- counselling to promote informed choices
when is genetic counselling needed
- diagnosing
- risk determination of carriers
- plan gestation in carriers
- if prenatal tests reveal abnormality or risk
why generate genetic maps
- determine whether mutations affect different genes
- clone genes and their map positions
- predict inheritance patterns.
- genome sequencing projects
linkage with no exchange
ratio of 3A_B_:1aabb
linkage with exchange
linkage on a single pair of homologs with exchanging occurring between non-sister chromatids.
the linked genes can be separated by recombination, shuffling alleles.
depends on how often recombination occurs and how close the genes are
coupling phase
cis. 2 dominant alleles of different genes on same homolog
repulsion phase
trans. 2 2 dominant alleles of different genes do not stay together. heterozygous on each homolog
recombination frequency
proportion of recombination gametes depending on how often the cross overs occurs
RF = (no. of recombinants / total progeny) x100
map distance
percentage of recombinant offspring correlated with the distance between two genes. map units mu or centiMorgan cM.
mapping human genes
mapping genes is difficult with small number of progeny. analysis to pedigree where the data from pedigrees can be combined using LOD (logarithm of odds) scores
interference
interference between double cross-overs can occur, where one cross-over interferes with another occurring nearby, therefor reducing the chance of recombination nearby.
calculating interference
calculate expected number of cross-overs
- chance of c.o. of the two inner genes and multiply them together x the progeny
- add up observed cross overs
- observed/ expected = coefficient of coincidence
Interference = 1- C
positive interference
less double crossovers than expected I>0, C<1
negative interference
more double crossovers than expected I<0, C>1
mitotic recombination
in mitosis homolog chromosomes do not pair to form bivalence, therefore cross over do not occur. however can occur producing new combinations of alleles. giving rise to a path of tissue with characteristics different to the rest of the mitotic clones
physical exchange between chromosomes
recombination combinations can be demonstrated by markers so that they can be distinguished cytologically.
intragenic recombination
recombinations can occur within genes
e.g. lozenge eye. trans-heterozygote (2 different mutations in same gene) for 2 alleles with mutant phenotype
