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Q. In an association analysis the following reQsults was obtained from one of the investigated markers....

Q.

In an association analysis the following reQsults was obtained from one of the investigated markers.

A1A1 A1A2 A2A2
Controls 1250 670 80
Cases 533 400 67

a) Test for HW in the controls. b) What is the MAF in the controls? c) Which is the risk allele? Test for association of d) genotypes, and e) alleles. f) Calculate the odds-ratio (OR).

Q.

A plant species has an average height of 100 cm. In this exists a recessive “dwarf allele”, h, at a locus that gives a height of 50 cm. Two pure lines are crossed, i.e. H/H x h/h and then the F1 is intercrossed. A) Calculate the variance in the F2 population. B) What are the a and d values of the H-locus? C) What are VA and VD in the F2 population? Now consider two pure lines, 100 and 50 cm high, but where the difference is due to 25 additive loci with equal effect. D) Calculate VA for an F2 population from these lines. E) If the F2 are populations grown in an environment that generates a VP of 100 cm2. What is h2 in the respective F2 population.

Q.

The number of chiasmata was counted in a specific chromosome of Z. dingbats. The following results were obtained: 1 chiasma 200 cells, 2 chiasmata 600 cells and 3 chiasmata 200 cells. A) Calculate the average number of chiasmata, and the map distance of the chromosome. B) What is the recombination frequency between two loci on the opposite ends of the chromosome? The chromosome is 100 Mb long. Assume that crossovers are occurring with equal probability over the chromosome. Consider two loci A and B that are situated 10Mb from each other. C) What is the map distance of this region? D) What is the recombination frequency of this region? (Assume that the distribution of crossovers observed is the true one.)

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In case-control genetic association studies, cases are subjects with the disease and controls are subjects without the disease and at the time of case-control data collection, information about secondary phenotypes is also collected.In genetic association studies, the deviation from Hardy-Weinberg proportion (HWP) or (HW) of each genetic marker is assessed as an initial quality check to identify questionable genotypes(disease causing genes). Using only controls for testing HWP or HW can result in a highly inflated type I error rate for the disease- or phenotype-associated variants. So, two approaches, the likelihood ratio test (LRT) approach and the mixture HWP (mHWP) exact test were proposed for testing HWP in samples from case-control studies.

Minor allele frequency (MAF) - is the frequency of the least often occurring allele at a specific location.

Risk allele in terms of a disease, this is the allele that confers a risk of developing the disease.

Test for association of genotype is categorised into 4 headings -

  • Basic Allelic Tests- association with individual alleles are tested.
  • Genotypic Tests - refers to testing of genotype.
  • Additive Model - testing is designed to reveal associations which depend additively based on the allele classification .
  • Dominant Model-to test the association of having one dominant allele.
  • Recessive Model -to test association of having recessive allele.

Test for association of Allele - Chi square test can be used as a test for association of allele.

Odd ratio is measure of association between exposure and an outcome .In short it is a measure to identify risk allele or disease causing genes.


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