Reference no: EM133431201

Questions: Imagine that you are a geneticist at a hospital, and you are given a ?le for a patient who has the following history.

The female patient is 30 years old. Her second pregnancy had to be terminated because the baby she was carrying had abdominal wall defects (exomphalos) as well as enlarged organs inside the abdomen (visceromegaly). In contrast, her first pregnancy was normal, and the baby was born without any complications. Her husband's family has no history of the condition and neither does her own family.

To gain insight into what the cause of the malformed baby could be, you order whole exome sequencing of the patient's DNA. You get back the results and find out that the patient is heterozygous at four loci (candidate genes 1-4); each with SNPs that are not common in the general population. Their sequences are found in the appendix (see below). Your goal as a geneticist is to determine which gene has the causative mutation that led to her baby having the malformations and advise the patient about her options.

1. What does whole exome sequencing achieve? How is it different from whole genome sequencing?

2. Conduct a BLAST search using the candidate gene sequences. What are the identities of each of the candidate genes? What do they encode?

3. What kind of changes are present in the sequences of each of the candidate genes? What is the consequence of each mutation?

4. Is the mutation in the protein coding region of the gene? If it is, how would you experimentally determine that this is the protein coding region?

5. Based your conclusions, which one is the most likely to be the causative mutation that led to the fetal malformations? Explain your reasoning and make a convincing case.

6. Is there a disorder or syndrome associated with the gene you chose in 4? If there is, what is it?

7. To con?rm that the patient has a mutation in the suspected gene(s), what molecular

technique could you use that doesn't involve sequencing?

8. Now that you have identified a candidate gene, you decide to test whether the patient's husband, mother or father carry the mutation. What is the simplest way to test this?

9. It turns out that neither her husband nor her mother has the mutation, while her father does (he is also heterozygous). Since the patient inherited the mutation from her father, explain the mechanism of inheritance of the gene.

10. Why did the affected baby have phenotypes, while neither the patient nor her father, despite having the mutation, have any phenotypes?

11. If the patient wants to try and have another child, how would you advise that she proceed? What is are some reasonable solutions?