Methods of identifying point mutations in a genome that cause or accelerate disease

Abstract

The invention relates to a method for identifying inherited point mutations in a targeted region of the genome in a large population of individuals and determining which inherited point mutations are deleterious, harmful or beneficial. Deleterious mutations are identified directly by a method of recognition using the set of point mutations observed in a large population of juveniles. Harmful mutations are identified by comparison of the set of point mutation observed in a large set of juveniles and a large set of aged individuals of the same population. Beneficial mutations are similarly identified.

What is claimed is:  
     
         1 . A method of identifying genes which carry a harmful allele that is a secondary risk factor that accelerates the appearance of a disease, comprising: 
 a) identifying the inherited point mutations which are found in the genes or portions thereof of an early onset proband population, and determining the frequency with which each point mutation occurs;    b) identifying the inherited point mutations which are found in the genes or portions thereof of a late onset proband population, and determining the frequency with which each point mutation occurs;    c) comparing the frequencies of point mutations which are found in a selected gene or portion thereof in the early onset proband population with the frequencies of the same point mutations in said selected gene or portion thereof of the late onset proband populations; wherein a significant increase in the frequencies of one or more point mutations in the early onset proband population relative to the late onset proband population indicates that said gene carries a harmful allele which is a secondary risk factor which accelerates the appearance of disease.    
     
     
         2 . A method of identifying genes which carries a harmful allele that is a secondary risk factor that accelerates the appearance of a disease, comprising: 
 a) identifying the inherited point mutations which are found in the genes or portions thereof of an early onset proband population, determining the frequency with which each point mutation occurs, and calculating the sum of the frequency of all point mutations identified for each gene or segment;    b) identifying the inherited point mutations which are found in the genes or portions thereof of a late onset proband population, and determining the frequency with which each point mutation occurs, and calculating the sum of the frequency of all point mutations identified for each gene or segment;    c) comparing the sum frequency of point mutations which are found in a selected gene or portion thereof of the early onset proband population calculated in a) with the sum frequency of point mutation which are found in the same gene or portion thereof of the late onset proband population calculated in b), wherein a significant decrease in the sum frequency of point mutations in the late onset proband population indicates that said selected gene carries a harmful allele which is a secondary risk factor that accelerates the appearance of a disease.