Morbid Anatomy of the Human Genome

ABSTRACT

Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart from the beaten path; nor is there any better way to advance the proper practice of medicine than to give our minds to discovery of the usual law of Nature by careful investigation of cases of rarer forms of disease. For it has been found, in almost all things, that what they contain of useful or applicable is hardly perceived unless we are deprived of them, or they become deranged in some way. (Taken from Garrod1 quoting a letter written by William Harvey in 1657 to emphasize the value of studying human variants.)

INTRODUCTION

The Morbid Anatomy of the Human Genome is a list of mapped loci for which there is a known clinical association (Fig. 2-1). It is derived from the Synopsis of the Human Gene Map which was published in the 7th edition of MMBID and which is available with Online Mendelian Inheritance in Man (OMIM), a continuously updated catalog of genetic disorders and genes (http://www.ncbi.nlm.nih.gov/omim). The gene map and morbid map are periodically published as part of Mendelian Inheritance in Man (Johns Hopkins University Press, 12th edition, 1998).

The morbid map provides a view of the genome with a focus on disease. By indicating where each mapped disease is located along each chromosome, it provides a ready reference associating cloned genes with diseases, an overview of the range of diseases associated with mutations in a particular gene or gene family, insight into gene function based on the disease etiology and vice versa, and a ready list of phenotypes relevant to cytogenetic rearrangements and contiguous gene syndromes. The OMIM Morbid Map can be accessed at http://www.ncbi.nlm.nih.gov/Omim/searchmorbid.html (this is Table 2-2 in MMBID, 8th edition).

Table 2-1

The fields of the Morbid Map are as follows:

1. Location. Chromosomal location.

2. Symbol. Gene or locus symbol(s).

3. Status. The certainty of mapping is represented by 3 symbols:

   C = confirmed

   P = provisional

   L = limbo or tentative

4. Locus Name. Title of gene or locus.

5. MIM#. This is a unique ...