Biochemistry 158/258

A Human Genome Stained by Fluourescent in Situ Hybridization

Genomics, Bioinformatics & Medicine

Doug Brutlag


Most of the SNP variations associated with diseases in genome-wide association studies do not cause the disease, but instead, these SNPs serve as genetic markers that are linked to genes which are involved in the disease. Ongoing research is attempting to sequence these genes in patients and in controls to find the actual variations in these genes that do, in fact, cause the disease.

For this assignment I would like you to choose a simple Mendelian inherited disease other than those mentioned in class (Huntingtons, Parkinsons, cystic fibrosis, sickle cell) and describe what is known about the genetic variations that cause that disease.

You may search OMIM, dbSNP, dbVAR, ClinVar, HGMD, HGVS, SwissVar and other databases of genome variations that are associated with specific diseases to find an example of the kinds of mutations associated with the disease. Please describe how each of these variations cause the disease.

Is it by:

1) mutating the coding region of the protein

2) altering the gene expression by affecting the promoter

3) altering gene expression by affecting a transcription factor binding site

4) altering gene expression indirectly by mutating a transcription factor itself

5) altering copy number, hence changing gene expression levels

6) altering other regulatory sites (miRNA genes or target sites, lncRNA etc.)

7) altering splice signals etc.

Often there will be several types of mutations that can cause the disease. Please comment on all types that are known for your chosen disease.

Please remember that this is a research report, not a list of short answers. You should write full paragraphs on each of the types of causal mutations found.

© Doug Brutlag 2015