Methods for detecting genome-wide sequence variations associated with a phenotype
0 Assignments
0 Petitions
Accused Products
Abstract
The invention provides methods for determining genome-wide sequence variations associated with a phenotype of a species in a hypothesis-free manner. In the methods of the invention, a set of restriction fragments for each of a sub-population of individuals having the phenotype are generated by digesting nucleic acids from the individual using one or more different restriction enzymes. A set of restriction sequence tags for the individual is then determined from the set of restriction fragments. The restriction sequence tags for the sub-population of organisms are compared and grouped into one or more groups, each of which comprising restriction sequence tags that comprise homologous sequences. The obtained one or more groups of restriction sequence tags identify the sequence variations associated with the phenotype. The methods of the invention can be used for, e.g., analysis of large numbers of sequence variants in many patient samples to identify subtle genetic risk factors.
11 Citations
119 Claims
-
1-102. -102. (canceled)
-
103. A method for determining sequence information at the 5′
- and 3′
ends of a nucleotide fragment, comprising;
a) fragmenting a source nucleic acid to generate a plurality of nucleotide fragments;
b) inserting each nucleotide fragment of the plurality into a vector to generate circularised vectors comprising nucleotide fragments;
c) treating the circularised vectors comprising nucleotide fragments, wherein each nucleotide fragment in a circularised vector is cut at least twice to generate a linearised vector comprising the 5′ and
3′
ends of the nucleotide fragment and a separate internal sub-fragment of each nucleotide fragment;
d) linking the 5′ and
3′
ends of each nucleotide fragment of the linearised vector to generate a circularised vector comprising a shortened nucleotide fragment, wherein the internal sub-fragment of each nucleotide fragment has been removed;
e) generating sequence information from each of the shortened nucleotide fragments, wherein the sequence information is generated across both 5′ and
3′
linked ends of the nucleotide fragments. - View Dependent Claims (104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119)
- and 3′
Specification