Recombination Frequencies

1
Technology in the News
Genetics in the News
2
Your Future

• Today Sex Linkage, Linkage, Quiz through Chapter
  4,
• Friday Lecture 7, Chromosomal Mutations,
• work problems from the Chapters, answer
  questions,
• Monday Video (required), No Office Hours.
• Wednesday Finish Lecture 7, questions and
  answers, Quiz through Chapter 5,
• Friday Midterm I, through Chapter 4.

Will announce expanded office hour schedule
Friday.
3
Sex Chromosomes

• ... X and Y chromosomes that determine the
  sex of an individual in many organisms,
• Females XX
• Males XY

4
XY male
5
X Linkage

• the pattern of inheritance resulting from genes
  located on the X chromosome.

X-Linked Genes refers specifically to genes on
the X-chromosome, with no homologs on the Y
chromosome.
6
Blue is dominant.
P
x
Blue Female
Pink Male
Gametes
or
7
Gametes
or
F1
Blue Female
Blue Male
8
F1
x
Blue Female
Blue Male
Gametes
or
or
9
Gametes
or
or
F2
Blue Female
Blue Male
Blue Female
Pink Male
10
F2
Blue Female
Blue Male
Blue Female
Pink Male
3 1 Blue to Pink
1 1 Female to Male
11
P
x
Pink Female
Blue Male
Gametes
or
12
Gametes
or
F1
Blue Female
Pink Male
13
Gametes
or
or
F2
Pink Female
Pink Male
Blue Female
Blue Male
14
F2
Pink Female
Pink Male
Blue Female
Blue Male
1
1
1
1
1 1 Female to Male
15
Sex Linkage to Ponder

• Female is homozygous recessive X-linked gene,
• what percentage of male offspring will express?
• what percentage of female offspring will express
  if,
• mate is hemizygous for the recessive allele?
• mate is hemizygous for the dominant allele?
• Repeat at home with female heterozygous X-linked
  gene!

16
Sex-Linked vs. Autosomal

• autosomal chromosome non-sex linked chromosome,
• autosomal gene a gene on an autosomal
  chromosome,
• autosomes segregate identically in reciprocal
  crosses.

17
X-Linked Recessive TraitsCharacteristics

• Many more males than females show the phenotype,
• female must have both parents carrying the
  allele,
• male only needs a mother with the allele,
• Few (or none) of the offspring of affected males
  show the disorder,
• all of his daughters are carriers,
• half of the sons born to these daughters are
  carriers.

18
(No Transcript)
19
X-Linked Dominant

• Affected males married to unaffected females pass
  the phenotype to their daughters, but not to
  their sons,
• Heterozygous females married to unaffected males
  pass the phenotype to half their sons and
  daughters,
• Homozygous dominant females pass the phenotype on
  to all their sons and daughters,

20
(No Transcript)
21
Autosomal Dominant

• Phenotypes appear in every generation,
• Affected males and females pass the phenotype to
  equal proportions of their sons and daughters.

22
(No Transcript)
23
(No Transcript)
24
Pedigree for Very Rare Trait? kid with trait
1/2
1/2
Recessive?
--- Yes!
1/2 x 1/2 x ?
1/2 1/8
x 1/2 1/16
Autosomal?
X-Linked?
--- Yes!
25
Linkage

• Genes linked on the same chromosome may segregate
  together.

26
Independent Assortment
A
b
a
B
2n 4

A
A
a
B
b
B
a
b

27
MeiosisNo Cross Over
2n 1
A
a
Parent Cell
B
b
A
A
a
a
B
B
b
b
Daughter Cells Have Parental Chromosomes
28
MeiosisWith Cross Over
2n 1
A
a
Parent Cell
B
b
A
A
a
a
B
b
B
b
Daughter Cells Have Recombinant Chromosomes
29
Dihybrid Cross
phenotype genotype gametes genotype

• yellow/round
  green/wrinkled
• GGWW x ggww
• GW gw
• GgWw

P F1
30
Gamate Formation in F1 Dihybrids P GGWW x
ggww, Independent Assortment
F1 Genotype GgWw
G g W
w
alleles gametes
GW
Gw
gW
gw
probability
31
How do you test for assortment of alleles?
F1 GgWw
Testcross phenotypes of the offspring indicate
the genotype of the gametes produced by the
parent in question.
32
Test CrossGgWw x ggww
GW (.25)
gw (1)
GgWw (.25)
Gw (.25)
gw (1)
G gww (.25)
gW (.25)
gw (1)
ggWw (.25)
gw (.25)
gw (1)
ggww (.25)
33
Test CrossGgWw x ggww
GW (.25)
gw (1)
GgWw (.25)
Gw (.25)
gw (1)
Ggww (.25)
gW (.25)
gw (1)
ggWw (.25)
gw (.25)
gw (1)
ggww (.25)
34
Recombination Frequency

• or Linkage Ratio the percentage of recombinant
  types,
• if 50, then the genes are not linked,
• if less than 50, then linkage is observed.

35
Linkage

• Genes located on the same chromosome do not
  recombine,
• unless crossing over occurs,
• The recombination frequency gives an estimate of
  the distance between the genes.

36
Recombination Frequencies

• Genes that are adjacent have a recombination
  frequency near 0,
• Genes that are very far apart on a chromosome
  have a linkage ratio of 50,
• The relative distance between linked genes
  influences the amount of recombination observed.

37
a
b
a
c
38
Linkage RatioP GGWW x ggwwTestcross F1 GgWw
x ggww

• recombinant
• total progeny

x 100 Linkage Ratio
Units mu (map units) - or - cm
(centimorgan)
39
a
b
a
c
40
Fly Crosses(white eyes, minature, yellow body)
Study Figs 4.2, 4.3, and 4.5

• In a white eyes x miniature cross, 900 of the
  2,441 progeny were recombinant, yielding a map
  distance of 36.9 mu,
• In a separate white eyes x yellow body cross, 11
  of 2,205 progeny were recombinant, yielding a map
  distance of 0.5 mu,
• When a miniature x yellow body cross was
  performed, 650 of 1706 flies were recombinant,
  yielding a map distance of 38 mu.

41
Simple Mapping

• white eyes x miniature 36.9 mu,
• white eyes x yellow body 0.5 mu,
• miniature x yellow body 38 mu,

42
X-Linked Dominantexamples (OMIM)

• HYPOPHOSPHATEMIA Vitamin-D resistant
  Ricketts,
• LISSENCEPHALY smooth brain,
• FRAGILE SITE MENTAL RETARDATION mild
  retardation,
• RETT Syndrome neurological disorder,
• More on OMIM

43
Assignments

• Read from Chapter 3, 3.6 (pp. 100-106),
• Master Problems3.12, 3.15, 3.20,
• Chapter 4, Problems 1, 2,
• Questions 4.1 - 4.4, 4.6, 4.7, 4.9, 4.11 -4.14,
  4.19 - 4.20 a,b,c,d.

44
Do We have to Learn More Mapping Techniques?

• Yes,
• three point mapping,
• Why,
• Certainty of Gene Order,
• Double crossovers,
• To answer Cyril Napps questions,
• and, for example over 4000 known human diseases
  have a genetic component,
• knowing the protein produced at specific loci
  facilitates the treatment and testing.

45
Classical Mapping
Cross an organism with a trait of interest to
homozygous mutants of known mapped genes.

• Then, determine if segregation is random in the
  F2 generation,
• if not, then your gene is linked (close) to the
  known mapped gene.

What recombination frequency do you expect
between the target and HY2?
What recombination frequency do you expect
between the target and TT2?
46
Gene Order

• It is often difficult to assign the order of
  genes based on two-point crosses due to
  uncertainty derived from sampling error.
• A x B 37.8 mu,
• A x C 0.5 mu,
• B x C 37.6 mu,

47
Double Crossovers

• More than one crossover event can occur in a
  single tetrad between non-sister chromatids,
• if recombination occurs between genes A and B 30
  of the time (p 0.3), then the probability of
  the event occurring twice is 0.3 x 0.3 0.09, or
  nearly one map unit.
• If there is a double cross over, does
  recombination occur?
• how does it affect our estimation of distance
  between genes?

48
Three Point Testcross

• Triple Heterozygous
• (AaBbCc )
• x
• Triple Homozygous Recessive
• (aabbcc)

49
Three Point Mapping Requirements

• The genotype of the organism producing the
  gametes must be heterozygous at all three loci,
• You have to be able to deduce the genotype of the
  gamete by looking at the phenotype of the
  offspring,
• You must look at enough offspring so that all
  crossover classes are represented.

50
w g d

• Representing linked genes...
• W G D
• w g d
• x
• w g d
• w g d

P
WwGgDd
Testcross
wwggdd
51
w g d

• Representing linked genes...
• w g d
• x
• w g d
• w g d

P
WwGgDd
Testcross
wwggdd
52
Phenotypic Classes
W-G-D-
W-G-dd
W-
W-gg-D
W-gg-dd
wwG-D-
wwG-dd
ww
wwggD-
wwggdd
53

Arbitrarily name regions between genes
W-G-D-
179
Parentals
wwggdd
173
W-G-dd
46
Recombinants 1 crossover, Region I
I
II

• W G D
• w g d

wwggD-
52
wwG-D-
22
Recombinants 1 crossover, Region II
W-gg-dd
22
W-gg-D
2
Recombinants, double crossover
wwG-dd
4
54

I
W-G-D-
179

• W G D
• w g d

Parentals
wwggdd
173
W-G-dd
46
Recombinants 1 crossover, Region I
wwggD-
52

Region I
wwG-D-
22
Recombinants 1 crossover, Region II
W-gg-dd
22
46 52 2 4 500
x 100
W-gg-D
2
Recombinants, double crossover
wwG-dd
4
20.8 mu
Total 500
55

II
20.8 mu
W-G-D-
179

• W G D
• w g d

Parentals
wwggdd
173
W-G-dd
46
Recombinants 1 crossover, Region I
wwggD-
52

Region II
wwG-D-
22
Recombinants 1 crossover, Region II
W-gg-dd
22
22 22 2 4 500
x 100
W-gg-D
2
Recombinants, double crossover
wwG-dd
4
10.0 mu
Total 500
56
10.0 mu
20.8 mu

• W G D
• w g d

0.1 x 0.208 0.0208
NO GOOD!
6/500 0.012
57
Interference

• the effect a crossing over event has on a second
  crossing over event in an adjacent region of the
  chromatid,
• (positive) interference decreases the
  probability of a second crossing over,
• most common in eukaryotes,
• negative interference increases the probability
  of a second crossing over.

58
Gene Order in Three Point Crosses

• Find either double cross-over phenotype, based on
  the recombination frequencies,
• Two parental alleles, and one cross over allele
  will be present,
• The cross over allele fits in the middle...

59

2001
A-B-C-
1786
aabbcc
46
A-B-cc
Which one is the odd one?
52
aabbC-
990
aaB-cc
887
A-bb-C-
600
A-bb cc
589
aaB-C-
60

Region I
A-B-C-
2001
aabbcc
1786
A-B-cc
46
aabbC-
52
aaB-cc
990
I
A-bb-C-
887

• A C B
• a c b

A-bb cc
600
aaB-C-
589
61

Region II
A-B-C-
2001
aabbcc
1786
A-B-cc
46
aabbC-
52
aaB-cc
990
28.4 mu
II
A-bb-C-
887

• A C B
• a c b

A-bb cc
600
aaB-C-
589