Genes and Disease

Written by Núria López


Many diseases are caused by mutations in the DNA. In some cases the disease is hereditary (i.e. it is inherited through different generations in a family). These diseases are usually caused by mutations in a single gene that makes the protein it encodes not to function properly or not to function at all. These are called Mendelian diseases or hereditary diseases, and can have different type of inheritance (Dominant, Recessive or X-linked).

Some examples of these diseases are: Cystic fibrosis, neurofibromatosis, some types of deafness, Duchene muscular dystrophy, some types of diabetes...
Other types of diseases are also due to mutations or alterations in the DNA but are not Mendelian diseases, for example, cancer is caused by mutations in some key genes (onco-genes and tumour suppressor genes), although this mutations are usually not inherited but acquired during the life time (somatic mutations). Complex diseases, for example, diabetes, atherosclerosis, cancer, and neurodegeneration, are also due to variations in the DNA, but in that cases is not a single mutation in a particular gene that cause the disease but a number of factors, including several modifications in the DNA in conjunction with environmental factors that determine the risk to suffer the disease.
It is important to know the genes implicated in hereditary diseases, since this knowledge can lead to improvements in disease prevention, diagnosis and treatment. The usual process followed to identify disease genes and mutations is the linkage analysis in DNA samples of affected and non-affected families members with the disease, that is to analyse markers along the genome to identify a region linked to the disease. Once the region is identified, it will be necessary to do mutation analysis to detect the causative mutation leading to the disease.


There is big amount of information available in databases that can be useful to find genes and mutations involved in diseases.

We may want to respond questions like:

Do we know the causative gene for a particular disease?

Which disease mutations have been found in a particular gene?

What genes are in a particular region that we have found linked to the disease we are studying?

And which of all these genes in the linked region is the more likely to be causing the disease of interest?

Databases and Catalogs

Several databases help us to find information related to diseases, mutations and polymorphisms.

We can find information about a particular disease for which we already know the gene:

Question: Which type of inheritance follows Cystic Fibrosis? Which symptoms characterize this disease?

Note: use OMIM

Question: Which is the causative gene of Cystic Fibrosis?

Note: you can use OMIM or NCBI Entrez Gene

Question: How many mutations have been found in this gene?

Note: use HGMD

For some disease we don't know yet the causative gene, but the linkage analysis has been done and we know the region of the genome that is linked to that disease.

Question: Find the genomic localization of Nephropathy-hypertension.

Note: use NCBI Entrez Gene

Prediction of disease genes

Imagine we can do some computational analysis that will predict which is the causative gene for the disease we are studying. We would then skip a lot of work on mutation analysis. There have been some recent works on that direction. These works exploit the big amount of data we have currently on genes and diseases to predict which other genes are the more likely to cause other diseases.

Question: Find the candidate genes for Nephropathy-hypertension using the three servers.

Question: Imagine you are looking for a new disease gene and you have found that it is linked to the region 13q12, look for candidate genes in this region using DGP.

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