Download doc Summer 2010 Lecture 3

BIOL 202
5.5 Genetic Mapping
There are a number of genes in the mtDNA
- many involved with energy production
- some play roles in heredity
- chromosomal inheritance is 50% male and 50% female
- organelle DNA: male contribution is low
o random distribution—no spindle dividing it
 get a segregation of mitochondria into 2 daughters
 if the dominant allele is on the L at time of division and
recessive on R, then one daughter will only have
dominant and one only recessive
 not so much of a problem if somatic cells
 but if germ cell, and 1 egg only has recessive alleles
and 1 only dominant alleles, may be problematic
o see this in variegated plants
 genes that encode the machinery for the
green pigments are in chloroplasts
 division causes a mosaic
o mostly end up with at 5050 split
o areas that are white, the
chloroplasts didn’t get the
dominant green-pigmentmaking allele: most parts
are variegated; parts that
are all green have all
dominant; parts that are
all white have all
recessive
- important for human diseases
o many don’t seem to have nuclear heritability—appear to be completely
maternally-related
 map to mitochondria
 if a dominant mutation in a mother’s mitochondria, will pass it
to ALL of her offspring
 the males never pass on the mutation to his kids
 all the daughters/women will pass mutation on to all her
kids
- phenotype of mutations
o mitochondrial chromosome is tiny
o a lot are diseases related to energy and metabolism
Scientific basis
- Model organism is neurospora
o When they sporulate, all contain an ascus with 8 indiv haploid spores
all in a linear array
BIOL 202
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Form like this because of cell division
 Divides in vertical plain
  can tell where the cells came from
 can also follow chromosomes and how they move
because of this ordered division
o can mark a chromosome with dominant allele, e.g. with GFP
 by following ascus, can see where dominant allele is
Cytoplasmic inheritance
o Poky phenotype
 Poky spores grow slowly
 Inheritance of poky wasn’t nuclear
 Found it’s from mitochondria
 Saw that females with poky passed it onto all spores but
chromosomes were moving properly
 But when males with poky, didn’t pass the gene on—
chromosomes still moving properly
  non-nuclear inheritance
Genetic Mapping
- genes move independently because on different chromosomes or far apart on
the same chromosome
- when genes move together, are considered genetically linked
o physically linked, too bc on single piece of DNA
- created genetic maps of linkages
- Studying genes on plants
o Found many single-gene traits
 Some linked, some not
 Some genes (linked) didn’t move as Mendel predicted
 Could count chromosomes: individual linkage groups
mapped to different chromosomes
- Bateson and Punnett
o Tried to replicate Mendel’s experiments with different pea plants
 Mated purebreeding red flower and long pollen and
purebreeding white flower and short pollen pea plants
 Expected (phenotypes move independently
o  all in F1 were red with long pollen
o in F2, got a mix of styles
 Actual
o Got something very different: no 9:3:3:1
o 2 of 383  not due to chance
o the phenotypes are moving together
 get preference for parental phenotypes;
recombinant phenotypes relatively rare
- Why recombination or lack therof?
o To prove linkage, did a test cross of RrLl and rrll
 Allows to see the parental chromosome phenotype
BIOL 202
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End up with red, long and white, short phenotypes if the
chromosomes don’t break
 If the chromosomes break, could get cross between the 2
chromosomes  recombinant phenotypes
 See mostly parental phenotype and very little recombinant
Recombinant frequency (RF)
o = (# of recombinants)/(total number of progeny)
o 1% recombinant frequency = 1 centimorgan (1 cM) = 1 genetic map
unit (m.u.)
o RF of 2 unlinked genes is 50%
o For linked genes, is less than 50%
Morgan did most of the linkage analysis studies, on drosophila
o Found easily seen phenotypes; mapped them
 Single genes, straight up dominance; but also linked genes
 Can combine maps to figure out order of genes
Drosophila genetics
- nomenclature:
o + = WT
o lowercase = recessive
- crossing a recessive (purple eyed, vestigial winged) with a dominant (red eyed
and normal winged) gives a normal fly in F1
- can see crossovers
- recombination doesn’t occur at the same rate over distances
- if genes A, B and C; and if A and B are physically close to each other, less
likely to get a recombination between A and B
Note: when unclear if 2 genes are on the same chromosome, use “” to denote this (e.g.
RRLL)
If on same chromosome, use “;” (e.g. RR;LL)
If on the same chromosome, use a “/” (e.g. RR/LL)
Three point testcross
- can look at 3 genes at one time
o e.g. vermillion (recessive to WT)
 cv controls existence of a vein on a fly’s wings
 ct is a cut mutant: wing has a cut in it
o cross normal red-eyed, veined trihybrid female with recessive all
 should end up with a 1:1:1:1:1:1:1:1
 ended up with mostly ones like mom
 cv and ct is 6.4 m.u. apart; ct and v are 13.2 m.u. apart
- Recombination between 2 genes is invisible without a 3rd gene in between
them
o Ones with least frequency would have had double recombinance
o Because of this, may end up marking as WT even if there is some
crossing over, if doesn’t appear in phenotype
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2 tightly linked genes (i.e. no crossing over), always end up with parental phenotype
Centromere mapping with linear tetrads
- in neurospora, can tell where the recombination occurred
- can dissect out the spores and count recombinants
Chi-square analysis and linkages
- non-significant p value means the genes are linked
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