L3 Mendelian Genetics 2

Front 1

What are the deviations from mendelian inheritance?

Back 1

• Non-independent assortment

– e.g. linkage (genes on same chromosome)

• Non-Mendelian segregation of phenotypes

– e.g. complex gene interactions

• These scenarios will result in ratios thatdiffer from the Mendelian cases

Front 2

How do we identify such deviations?

Back 2

• Are these different from what is expected?

– Are the differences big?

What is considered big?

– What is the probability that these differences could happen bychance?

• Calculate answers to these questions using the x2 Test

Front 3

What does the chi2 test show?

Back 3

• Compare observed versus expected results. Are theydifferent and is that difference by chance?

• The smaller the difference between observed andexpected, the more likely that it happened by chance.

• The c2 Test quantifies the probability that the differenceoccurred by chance.

• By scientific convention, a probability value of less than5% indicates that the difference did not occur by chance;i.e. it’s a significant difference.

Front 4

What does the chi2 test mean?

Back 4

chi2 represents the magnitude of difference between expected and observed.

Front 5

How do you find the probability from the chi2 value?

Back 5

Use a chart that convert a c2 value to the probability that thedifference occurred by chance, for the degrees of freedom(dF) of the data.

Front 6

What is the degrees of Freedom (dF)?

Back 6

dF = number of values that can vary independently= number of data categories – 1= 2 - 1 = 1

Front 7

What is the null hypothesis?

Back 7

The null hypothesis is the expected result based on anassumption (e.g. 50 heads 50 tails - coin is not biased).

Front 8

What is the p-value?

Back 8

The p-value is the probability that the difference between theobserved and result happened by chance (e.g. probability of0.0003 getting 68 heads and 32 tails in 100 coin tosses).

Front 9

What happed is the observed results are very different from the expected?

Back 9

If the observed results are very different from expected, thecalculated p-value would be very low and the nullhypothesis is rejected, meaning that the observed results donot fit the underlying assumption

Front 10

What happens if the observed results are similar to the expected results?

Back 10

If the observed results are similar to expected as indicated bya high p-value, then the null hypothesis is upheld. Thisoutcome means that the expected result was obtained, whichfit the underlying assumptions

Front 11

What are the problems with studying human inheritance?

Back 11

Mendel’s peas – can do controlled matings

• Cannot control matings in humans

• Can only look at available families

– Pedigree analysis

• Not many offspring

– Few observations

Front 12

What happens in pedigree analysis?

Back 12

Look at family trees

• Determine pattern of inheritance (disease)

– Dominant or recessive?

– Chances of being carriers or affected

Front 13

What are the features of human chromosomes?

Back 13

• 2 matching (homologous)sets of chromosomes*

• Females have two Xchromosomes

• Males have X and Ychromosomes

• Non-sex chromosomesare called autosomes

Front 14

What are the hallmarks of autosomal inheritance?

Back 14

• Disease appears in progeny of unaffected parents(skip generations)

• Affected progeny can be male or female (autosomal,not sex-linked)

• Consanguineous (parents who are related) matingsare more likely to produce progeny who arehomozygous recessive

Front 15

How can this be shown on a family tree?

Back 15

Front 16

What can we deduce having inferred autosomal recessive inheritance in the example of neonatal diabetes?

Back 16

• we can infer thegenotypes of individuals

• Affected individuals– genotype must be INSB/INSB– must have inherited one INSB allele from each parent

• Parents unaffected, therefore their genotype must be INSA/INSB

• Those who are unaffected but carry a disease-causing allele arecalled carriers

Front 17

What is the proability that this family's next child will have neonatal diabetes?

Back 17

Each pregnancy is an independent event. So thechances that the next child will have the disease isstill 1 in 4 (standard 3:1 Mendelian ratio).

Front 18

What are the hall marks of autosomal dominant inheritance?

Back 18

• Disease appears in every generation

• Affected progeny can be male or female(autosomal, not sex-linked)

• Affected individuals have affected parents

Front 19

What can we infer if we know a disease is autosomally dominantly inherited?

Back 19

• Unaffected individuals must be INSA/INSA

• The affected mother could be INSD/INSD or INSA/INSD

• The unaffected son must have received one INSA allele from each parent,which means the mother must be INSA/INSD

• The affected son must be INSA/INSD, because he would have received oneINSA allele from the father

• If the disease is rare, it is highly likely that the dominant disease-causingallele is also rare. Affected individuals will thus tend to be heterozygous.