BICD100-2019-1WI Day11 Slides PDF

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Testing if certain Hardy-Weinberg assumptions are being violated

Actual

# mice

Light

Dark

Dark Dark

11

0

11

Dark Light

6

0

6

Light Light

12

12

0

Total

29

12

17

H-W (exp)

# mice

Light

Dark

Dark Dark

4

0

4

Dark Light

13

0

13

Light Light

12

12

0

Total

29

12

17

Does this population follow HardyWeinberg equilibrium? a. Yes b. No

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Testing if certain Hardy-Weinberg assumptions are being violated Actual

# mice

Light

Dark

Dark Dark

11

0

11

Dark Light

6

0

6

Light Light

12

12

0

Total

29

12

17

H-W (exp)

# mice

Light

Dark

Dark Dark

4

0

4

Dark Light

13

0

13

Light Light

12

12

0

Total

29

12

17

Calculating the expected values Observed # of homozygous recessive p2 = 12 / 29 = 0.41 p = light allele = sqrt (0.41) = 0.64 Expected # of homozygous dominant q = dark allele = 1 - p = 1 - 0.64 = 0.36 q2 = 0.36 x 0.36 = 0.13 Expected # q2 = 0.13 x 29 = 4 (out of 29) Expected # of heterozygous 2pq = 2 x 0.64 x 0.36 = 0.46 Expected # 2pq = 0.46 x 29 = 13

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Two alleles of Mc1r for dark and light fur Different ways to determine if the observed numbers of a sample may be following Hardy-Weinberg equilibrium 1.

We can start from the homozygous recessive sub-population like we just did

2.

If we have full genotypes (i.e. able to distinguish between AA and Aa), we can also start from the homozygous dominant sub-population

3.

Or we can calculate p2 + 2pq + q2 and see if it deviates a lot from 1

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How do we determine which assumption(s) are being violated? For our example of the dark vs. light rock pocket mice, which Hardy-Weinberg assumption is most likely being violated (or violated in the most significant way)?

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Testing if the “no selection” assumption is being violated

Science (2013) 339: 1312-1316

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Progression of the course so far

Previously … •

Elephant poachers and King Tut: Inheritance of molecular markers such as STRs

•

Sickle-cell anemia: Genetics of traits controlled (for the most part) by single genes

•

Mouse coat color: Genetics of complex traits controlled by more than one genes

•

Independent assortment: Two or more genes on different chromosomes

Moving forward … •

Genetic linkage: Two or more genes physical close together on the same chromosome

•

Mouse coat color: Using molecular markers and genetic linkage to help identify genes for complex traits

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Genetic linkage and gene mapping

What we found confusing and/or interesting

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What we found confusing and/or interesting

“The part about distance between genes was very confusing.” “I do not understand linkage. I had a really hard time with the first question and I still do not really understand it or my answer. I think the m.u. are very interesting. I have a really hard time retaining information reading from a textbook. I understand better in lecture, which is why I think I have a hard time with the pre labs that are only reading form the book.” “The textbook mentions that chromosome mapping can be made more efficient and accurate with the aid of computers, but what is the principle/ theory by which the programmers used in order to write an algorithm for such program? Do they also used the "recombination frequency" method used by Morgan and Sturtevant, except that the computation is now automated?”

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Genes on different chromosomes vs. same chromosome

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Genes on different chromosomes vs. same chromosome

We have a cross between a heterozygous AB/ab with a homozygous recessive ab/ab. What is the ratio of parental type to recombinant type of offspring assuming that the two loci are on separate chromosomes? What is the ratio assuming that the two loci are closely linked on the same chromosome (no recombination)? Different chromosomes

Same chromosome

parental : recombinant

parental : recombinant

a.

3:1

1:1

b.

1:1

1:0

c.

1:2:1

1:2

d.

1:1:1:1

1:0:0:1

e.

9:3:3:1

5:1:1:1

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Genes on different chromosomes vs. same chromosome

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Recombination or crossing-over happens during meiosis

Crossing-over

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Overview of recombination

(Site of recombination)

(Rec8 and other proteins)

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Genetic linkage

ib.berkeley.edu/courses/ib162/Linkage.htm

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Location of recombination Genes R and T are on the same chromosome. Be tracking R and T phenotypes, which recombination event(s) be observed? + represents wild type alleles.

A

r

t

r

t

B

C

+

+

+

+

a. Position A b. Position B c. Position C d. Positions B and C e. All of the above BICD 100 | 16

Location of recombination Genes R and T are on the same chromosome. At which position(s) could recombination event(s) occur? + represents wild type alleles.

A

r

t

r

t

B

C

+

+

+

+

a. Position A b. Position B c. Position C d. Positions B and C e. All of the above BICD 100 | 17

Genetic linkage Undetected crossing-over

ib.berkeley.edu/courses/ib162/Linkage.htm

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Frequency of recombination: How far genes are located

no crossover observed

Recombination frequency = map unit (m.u.) = centiMorgan (cM) ib.berkeley.edu/courses/ib162/Linkage.htm

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How do we tell if two genes are linked? If A/A · B/B is crossed with a/a · b/b and the F1 is testcrossed (with a/a · b/b), what percentage of the testcross progeny will be a/a · b/b if the two genes are 10 m.u. apart? a.

25%

b.

40%

c.

45%

d.

50%

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Longer regions are more likely to have recombination

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Pair-wise comparisons between genes can generate maps

We have mapped the distance between genes A and B to be 5 m.u. and the distance between genes A and C to be 3 m.u. Do we need additional information to determine the relative positions of all three genes? a.

Yes

b.

No

c.

Not sure

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Pair-wise comparisons between genes can generate maps

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What can recombination tell us?

Alleles: Ay (yellow) > A (agouti) > at (tan) > a (nonagouti) Cross: Ay/at x at/a (with no wild-type A allele at all) But we get a very small number of wild-type agouti mice from this cross!

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What can recombination tell us?

In section, we will use recombination data to look at the chromosome structure of the yellow mutation

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Using molecular markers to map genes

1.

Use as a direct readout for a mutation in a gene that codes for a phenotype

2.

Use as loci on chromosome maps in additional to genes that code for phenotypes

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Molecular markers in disease diagnosis Circles = female Squares = male Filled in = affected Hollow = unaffected Which allele of the molecular marker M is linked with the disease allele in this family? a.

M’

b.

M’’

c.

M’’’

d.

M’’’’

P = disease allele p = non-disease allele BICD 100 | 27

Molecular markers in disease diagnosis Does having the M’’ allele mean that the person must also have the disease allele P? a.

Yes

b.

No

c.

Not sure

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Molecular markers in disease diagnosis Child 7 has the M’’ allele but not the disease. The most likely explanation is: 7

a.

Child 7 has a different father

b.

Crossing over between M and P happened in the father

c.

Crossing over between M and P happened in the mother

d.

Not enough information to tell

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Progression of the course so far

Previously … •

Elephant poachers and King Tut: Inheritance of molecular markers such as STRs

•

Sickle-cell anemia: Genetics of traits controlled (for the most part) by single genes

•

Mouse coat color: Genetics of complex traits controlled by more than one genes

•

Independent assortment: Two or more genes on different chromosomes

Moving forward … •

Genetic linkage: Two or more genes physical close together on the same chromosome

•

Mouse coat color: Using molecular markers and genetic linkage to help identify genes for complex traits

BICD 100 | 30...