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# Announcements - PowerPoint PPT Presentation

Announcements. 1. Answers to Ch. 3 problems 6, 7, 8, 12, 17, 22, 32, 35 posted - 230A. 2. Problem set 1 answers due in lab this week at the beginning of lab. Bring calculators to lab this week.

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### Announcements

1. Answers to Ch. 3 problems 6, 7, 8, 12, 17, 22, 32, 35 posted - 230A.

2. Problem set 1 answers due in lab this week at the beginning of lab. Bring calculators to lab this week.

3. Getting to know Flylab and testcross (lab 2) - printout of assignments from “notebook”, due this week at the beginning of lab.

4. Confusion with X-linked crosses: 1 cross or 2?

5. Seminar this Thursday - faculty research interests

Review of last lecture

1. Genetic ratios are expressed as probabilities. Thus, deriving outcomes of genetic crosses relies on an understanding of laws of probability, in particular: the sum law, product law, conditional probability (likelihood that one outcome will occur, given a particular condition), and the binomial theorum (used to determine particular combinations). Expand the binomial OR use factorial general formula to solve.

2. Statistical analyses (Chi square) - used to test the validity of experimental outcomes. In genetics, some variation is expected, due to chance deviation.

Outline of Lecture 6

I. Chi-square revisited

• Pedigree analysis- recessive vs. dominant traits

- solving pedigree problems

Chi-square formula

where o = observed value for a given category,

e = expected value for a given category, and sigma is the sum of the calculated values for each category of the ratio

• Once X2 is determined, it is converted to a probability value (p) using the degrees of freedom (df) = n- 1 where n = the number of different categories for the outcome.

Chi-square - Example 1

Phenotype ExpectedObserved

A 750 760

a 250240

1000 1000

Null Hypothesis: Data fit a 3:1 ratio.

degrees of freedom = (number of categories - 1) = 2 - 1 = 1

Use Fig. 3.12 to determine p - on next slide

X2 Table and Graph

Unlikely:

Reject hypothesis

likely

unlikely

Likely:

Do not reject

Hypothesis

0.50 > p > 0.20

Figure 3.12

Interpretation of p

• 0.05 is a commonly-accepted cut-off point.
• p > 0.05 means that the probability is greater than 5% that the observed deviation is due to chance alone; therefore the null hypothesis is not rejected.
• p < 0.05 means that the probability is less than 5% that observed deviation is due to chance alone; therefore null hypothesis is rejected. Reassess assumptions, propose a new hypothesis.

Conclusions:

• X2 less than 3.84 means that we accept the Null Hypothesis (3:1 ratio).
• In our example, p = 0.48 (p > 0.05) means that we accept the Null Hypothesis (3:1 ratio).
• This means we expect the data to vary from expectations this much or more 48% of the time.

Conversely, 52% of the repeats would show less deviation as a result of chance than initially observed.

X2 Example 2: Coin Toss

I say that I have a non-trick coin (with both heads and tails).

Do you believe me?

1 tail out of 1 toss

10 tails out of 10 tosses

100 tails out of 100 tosses

Tossing Coin - Which of these outcomes seem likely to you?

Compare Chi-square with 3.84 (since there is 1 degree of freedom).

a) Tails 1 of 1

b) Tails 10 of 10

c) Tails 100 of 100

Chi-square

a)

b)

c)

Don’t reject

Reject

Reject

X2 - Example 3

F2 data: 792 long-winged (wildtype) flies, 208 dumpy-winged flies.

Hypothesis: dumpy wing is inherited as a Mendelian recessive trait.

Expected Ratio?

X2 analysis?

What do the data suggest about the dumpy mutation?

II. Pedigree analysis

The complex study of human genetics - we don’t control human matings! Instead, we study family trees (pedigrees) to identify how traits are inherited.

Importance of Pedigrees

• Genetic counselors use them to identify risk of inherited illness.
• Genetic researchers use them to identify genes responsible for genetic disorders.
• If you or a relative keep good family records, they may some day be useful in tracking down a genetic illness in your family.

Recessive vs. Dominant TraitsAutosomal Recessive Traits

• Example: The albino (aa) mutation inactivates the gene for tyrosinase enzyme, which normally converts tyrosine to melanin in the skin, hair and eyes.
• Non-albino is AA or Aa
• Autosomal recessive traits can skip generations (appear in progeny of unaffected persons) and affect both males and females equally.

Autosomal Dominant Traits

• Example: Hypotrichosis, hair loss begins in childhood for both males and females.
• Autosomal dominant traits do not skip generations and affect both males and females.
• Some but not all children will be affected in every generation.
• Affected individuals are usually heterozygous since mutant allele is rare.

Achondroplasia Trait (DD or Dd)

D is a dominant allele interfering with bone growth.

Most people are dd.

OMIM: Online Mendelian Inheritance in Man (Humans)

• Compiled by team at Johns Hopkins University.
• Available at: www.ncbi.nlm.nih.gov/omim/
• Includes description of trait, mode of inheritance, molecular information.
• GREAT resource to find good reference for your presentation topic; database is easy to search and full of interesting information
• Another resource to find a topic from NPR programming: http://www.dnafiles.org/resources/index.html

Symbols used in human pedigree analysis

Male

Female

Consanguineous marriage

Mating

Parents and 1 boy, 1 girl (in order of birth)

Sex unspecified

Affected individuals

Heterozygotes for autosomal recessive

Death

Number of children of sex indicated

3

2

Propositus

Pedigree Problem 1 - albinism

How is this trait inherited? dominant or recessive?

What are most probable genotypes of each individual?

Solving Pedigree Problems

• Inspect the pedigree:
• If trait is dominant, it will not skip generations nor be passed on to offspring unless parents have it.
• If trait is recessive, it will skip generations and will exist in carriers.
• Form a hypothesis, e.g. autosomal recessive.
• Deduce the genotypes.
• Check that genotypes are consistent with phenotypes.
• Revise hypothesis if necessary, e.g. autosomal dominant.

What is the Mode of Inheritance?

Unaffected 2nd generation = rare, recessive trait

Deduce genotypes

Pedigree Example 3: Huntington’s Disease

unaffected

affected

Folksinger Woody Guthrie died of Huntington’s Disease.

Problem 3 Solution

HD = Huntington’s allele, hd = wildtype allele; data suggests Huntington’s Disease is autosomal dominant.

Inconclusive Pedigree

• Try deducing the genotypes using either autosomal recessive or autosomal dominant hypothesis; either one should work.