Genetic loci indicative of propensity for longevity and methods for identifying propensity for age-related disease

Abstract

This invention relates to genetic loci and methods for using polymorphic markers indicative of the propensity for longevity and the resistance to age-related disease. In particular, the invention defines a specified region of human chromosome 4 associated with exceptional longevity.

1 . A method for gathering data related to genetic factors that influence longevity, the method comprising: 
 amplifying a segment of DNA from a subject in a region between the genetic markers D4S1564 and D4S1572 on human chromosome 4; and    comparing the segment to a reference sequence.    
     
     
         2 . A method for gathering genetic information related to factors that influence longevity, the method comprising: 
 genotyping a segment of DNA from a subject in a region between the genetic markers D4S1564 and D4S1572 on human chromosome 4; and    comparing the segment to a reference sequence.    
     
     
         3 . The method of  claim 1  or  2  wherein the reference sequence is from a reference subject who has attained a reference age.  
     
     
         4 . The method of  claim 3  wherein the reference age is old age.  
     
     
         5 . The method of  claim 3  wherein the reference subject has attained at least 91 years of age.  
     
     
         6 . The method of  claim 5  wherein the reference subject has attained at least 95 years of age.  
     
     
         7 . The method of  claim 6  wherein the reference subject has attained at least 98 years of age.  
     
     
         8 . A method of evaluating a subject, the method comprising: 
 amplifying a segment of DNA from a subject, wherein the segment is located between the genetic markers D4S1564 and D4S1572 on human chromosome 4; and    comparing the amplified segment to a corresponding segment amplified from a relative of the subject who has attained a reference age.    
     
     
         9 . The method of  claim 8  wherein the reference age is old age.  
     
     
         10 . The method of  claim 8  wherein the relative of the subject has attained at least 91 years of age.  
     
     
         11 . The method of  claim 10  wherein the relative of the subject has attained at least 95 years of age.  
     
     
         12 . The method of  claim 11  wherein the relative of the subject has attained at least 98 years of age.  
     
     
         13 . The method of  claim 8  wherein the relative is a sibling.  
     
     
         14 . The method of  claim 1 ,  2 , or  8  further comprising evaluating the subject for Alzheimer's disease, cancer, or ocular disease.  
     
     
         15 . The method of  claim 1 ,  2 , or  8  further comprising evaluating the subject for a heart disease, cardiovascular disease, or stroke.  
     
     
         16 . A method of evaluating a subject, the method comprising: 
 genotyping a segment of DNA from a subject, wherein the segment is located between the genetic markers D4S1564 and D4S1572 on human chromosome 4; and    evaluating the subject for Alzheimer's disease, cancer, or ocular disease.    
     
     
         17 . The method of  claim 1 ,  2 ,  8 , or  16  wherein the segment is in a region between 108.0 to 112.6 cM on human chromosome 4.  
     
     
         18 . The method of  claim 17  wherein the segment is in a region between 108.0 to 109.0 cM on human chromosome 4.  
     
     
         19 . The method of  claim 17  wherein the segment is in a region between 109.0 to 112.6 cM on human chromosome 4.  
     
     
         20 . A method for gathering data related to genetic factors that influence longevity, the method comprising: 
 identifying a subject as a subject who has attained a reference age;    amplifying a segment of DNA from a subject in a region between the genetic markers D4S1564 and D4S1572 on human chromosome 4; and    recording genetic information about the amplified segment.    
     
     
         21 . A method for gathering data related to genetic factors that influence longevity, the method comprising: 
 identifying a plurality of human subjects who have attained a reference age;    amplifying a segment of DNA from each of the subjects, the segment comprising the genetic markers D4S1564 on human chromosome 4; and    recording genetic information about the amplified segment from each of the subjects.    
     
     
         22 . A method of mapping a genetic locus that affects longevity, the method comprising: 
 identifying a plurality of sibships in which at least two human siblings have attained a reference age;    genotyping DNA samples for a plurality of markers from each individual of the sibship; and    determining a LOD score for each marker of the plurality of markers.    
     
     
         23 . The method of  claim 20 ,  21 , or  22  wherein the reference age is an old age.  
     
     
         24 . The method of  claim 22  wherein at least one sibling is at least 95 years old if female and 91 years old if male.  
     
     
         25 . The method of  claim 22  wherein at least one sibling has attained 98 years of age.  
     
     
         26 . The method of  claim 24  wherein at least another sibling is at least 95 years old if female and 91 years old if male.  
     
     
         27 . The method of  claim 22  wherein the genotyping comprises genotyping using a plurality of markers on each chromosome.  
     
     
         28 . The method of  claim 22  wherein the method comprises a multipoint non-parametric analysis.  
     
     
         29 . The method of  claim 22  wherein the method comprises evaluating one or more of the individuals of the plurality of sibships for Alzheimer's disease, cancer, or ocular disease.  
     
     
         30 . The method of  claim 22  wherein the method comprises evaluating one or more of the individuals of the plurality of sibships for heart disease, cardiovascular disease, or stroke.  
     
     
         31 . A method of mapping a genetic locus that affects longevity, the method comprising: 
 providing nucleic acid samples from a population of human individuals who have attained a predetermined age; and    performing an association study that evaluates association between one or more genetic markers with an affected state of individuals in the population.    
     
     
         32 . The method of  claim 31  wherein the one or more markers are located on human chromosome four.  
     
     
         33 . The method of  claim 31  wherein the one or more markers are located on human chromosome four between D4S1564 and D4S1572.  
     
     
         34 . The method of  claim 31  wherein the predetermined age is 91 years if male and 97 years if female.  
     
     
         35 . The method of  claim 31  wherein the affected state is ability to live to the predetermined age.  
     
     
         36 . The method of  claim 31  wherein the affected state is Alzheimer's disease.  
     
     
         37 . The method of  claim 31  wherein the affected state is ocular disease.  
     
     
         38 . The method of  claim 31  wherein the affected state is cancer.  
     
     
         39 . The method of  claim 31  wherein the affected state is heart disease, cardiovascular disease, or stroke.