18. Molecular Genetic Tools

In an inheritance case, a man has died leaving his estate to be divided equally between 'his wife and his offspring.' His wife (M) has an adult daughter (D), and they argue that they should split the estate equally. As a young couple, however, the man and his wife had a son that they gave up for adoption. Two men have appeared, each claiming to be the son of the couple and therefore entitled to a one-third share of the estate. The accompanying illustration shows the results of DNA analysis for five genes for the mother (M), her daughter (D), and the two claimants (S1 and S2). Do the DNA results suggest that either man is likely to be the son of the man and his wife? Explain.

In Drosophila, loss-of-function Ultrabithorax mutations result in the posterior thoracic segments differentiating into body parts with an identity normally found in the anterior thoracic segments. When the Ultrabithorax gene was cloned, it was shown to encode a transcription factor and to be expressed only in the posterior region of the thorax. Thus, Ultrabithorax acts to specify the identity of the posterior thoracic segments. Similar genes were soon discovered in other animals, including mice and humans. You have found that mice possess two closely related genes, Hoxa7 and Hoxb4, which are orthologs of Ultrabithorax. You wish to know whether the two mouse genes act to specify the identity of body segments in mice.

How will you determine where and when the mouse genes are expressed?

In terms of molecular biology, what is a library?

If you had a sample of RNA to analyze, which of the following techniques would you most likely use?

What is CODIS? Describe the four most important features of genetic markers used in this system.

From GWAS, how do we know which genes are associated with a particular genetic disorder?

How does a positive ASO test for sickle-cell anemia determine that an individual is homozygous recessive for the mutation that causes sickle-cell anemia?

Compare and contrast the terms Paternity Index (PI) and Combined Paternity Index (CPI). How does each contribute to paternity determination?

What is the exclusion principle? How is it used in forensic genetic analysis and in paternity determination?

What is the statistical principle underlying genetic health risk assessment? Why are these assessments not predictive of disease occurrence?

You have constructed four different libraries: a genomic library made from DNA isolated from human brain tissue, a genomic library made from DNA isolated from human muscle tissue, a human brain cDNA library, and a human muscle cDNA library.

Which of these would have the greatest diversity of sequences?

You have constructed four different libraries: a genomic library made from DNA isolated from human brain tissue, a genomic library made from DNA isolated from human muscle tissue, a human brain cDNA library, and a human muscle cDNA library.

Would the sequences contained in each library be expected to overlap completely, partially, or not at all with the sequences present in each of the other libraries?

Using the genomic libraries, you wish to clone the human gene encoding myostatin, which is expressed only in muscle cells.

Assuming the human genome is 3x10⁹ bp and that the average insert size in the genomic libraries is 100 kb, how frequently will a clone representing myostatin be found in the genomic library made from muscle?

Explain the meaning of 'identity by descent' in the context of identifying genealogical relationship between individuals. In these analyses, why are segments of chromosomes (haplotypes) rather than individual STRs used to identify genetic relationships?

Using the genomic libraries, you wish to clone the human gene encoding myostatin, which is expressed only in muscle cells.

How frequently will a clone representing myostatin be found in the genomic library made from brain?