Topics

 Post-implantation genetic testing cont'd

 The significance of dominance- Mullers Morphs
 Epigenetics: genotype + environment = phenotype
 Environmental factors influence gene expression- modification of DNA and
histones

Status of our knowledge

Types of genetic testing

Post fertilization testing
 Amniocentesis
 Post fertilization and post implantation genetic testing, the fetus is formed

 Chemical analysis, DNA analysis, chromosomal analysis

 Standard karyotyping: squash the cells, look for aneuploidy

 Metabolic diseases
 Get both the maternal and paternal contribution to offspring
 Pre-implantation genetic testing
 Doing biopsies from the embryos (post fertilization)
 Embryos in 12-6 cell stage

 Extracting a single cell so can't do karyotyping

 Detect changes in copy number- mono and trisomies

 Transfer only unaffected embryos to the patient
Polar Body Testing
 Oogenesis in humans
 Can look at the genotype of the egg, can only look at maternal contribution
  Occurs technically prior to fertilization
 In females you have meiosis occuring but have only one viable product. The
other products are polar bodies.

 Meiosis
 During Meiosis I homologous chromosomes segregate
 It's random which one becomes the secondary oocyte or which one becoming
the polar body
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 Polar Body testing

 Day 1: second polar body removal (before fertilization)

 Day 1: first & second polar body removal
 Prior to fertilization so you know that the second polar body only has maternal
contribution
 Take the polar body, extract DNA, do PCR

Dominantly inherited traits

 Dominant inheritance bc present in every generation
 A lot of dominantly inherited traits, the allele responsible for the trait doesn't behave
a like a true dominant

 Ex: D/d = disease and D/D = more severe phenotype

 If it's a truly dominant allele, the heterozygote and homozygote should have identical
phenotypes
 Most dominantly inherited diseases in humans, are loss of function mutations
 Most dominantly inherited diseases are probably semidominant
 Huntingdon's is a true dominant (BRCA1 is not although the table suggests that)
 Loss of function mutations are fairly common and in most cases don't cause disease

Recessively inherited traits

What makes one allele dominant to another?

 Chalcone synthase: enzyme makes red pigment
 There are two different genes that make that enzyme because it's diploid
 If one copy of chalcone synthase is lost, the flower will still be completely red
 Happlosufficient: one copy sufficient for the process to function normally
 Transposon in the middle of the gene makes it a null
ATG

(null)
 Transposons: jumping genes
For Many proteins a reduction in amount has little effect on function
 Most loci are haplosufficient
Muller's Morphs
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 Fly geneticist, worked with Morgan (discovered gene mapping)

 Experiments on Drosophila melanogaster & pseudoobscura
 Exposing flies to x-rays, extracting salivary glands, doing squashes to look at the
chromosomes
 Salivary glands have polytene chromosomes, can do karyotyping, stereotypical
banding pattern
 Can identify changes in banding pattern that were associated with different
chromosomal changes
 Found examples of chromosomal deletions, duplications, inversions
 Translocations (nonreciprocal- lose or gain a piece of chromosome entirely, or
reciprocal chromosomes),
 Nonreciprocal: unequal exchange between non-homologous
chromosomes
 Reciprocal: nonhomologous chromosomes exchange at the same places
 Transpositions: movement of short DNA segments from one position in the
genome to another

 Amorph: complete loss of a functional product (null)

 Hypomorph: incomplete loss of function (leaky)
 Gain of function mutations: can be recessively inherited but more likely to be
dominantly inherited.
 Ex: Bar eye phenotype is the result of gene duplications
 Wildtype: 16A
 Bar type: duplicated 16A region, eyes are now abnormal, not all the
facets of the eye are forming

 Types of gain of function mutations: hypermorphs, neomorphs, antimorphs

 Hypermorphs: increase in normal function
 Neomorphs: new function often with a loss of the normal function
 Very rare
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 Ex: Often mutations in enzymes… an enzyme that normally binds to

glucose, not it binds to galactose
 Antimorphs: opposes the wt function (dominant negatives)

 The mutant gene product prevents the normal wildtype product from
functioning properly
 In proteins that have to homodimerize
 Ex: when protein forms a complex

Go through at the molecular level how to modify a gene and get these types

An allelic series of white alleles

 Hypomorphs
 Dosage effects in the female
 If you crossed apricot with white, paler apricot colored eye than the homozgyous for
the apricot
 Distinguish between hypomorphic with amorphic
 In amorphic it doesn't matter if you reduce function more
 In males they only have the apricot and the y chromosome,
 Males upregulate their x chromosomes