Methods to identify polynucleotide and polypeptide sequences which may be associated with physiological and medical conditions
First Claim
1. A method of determining whether a polynucleotide sequence of a non-human primate which has been or may be associated with a physiological trait in the non-human primate has undergone evolutionarily significant change relative to humans that exhibit the physiological trait to a lesser degree, comprising:
- (a) comparing the non-human polynucleotide sequence with the corresponding human primate polynucleotide sequence to identify any nucleotide changes, wherein the polynucleotide sequence is selected from the group consisting of ICAM-1 polynucleotide sequence, ICAM-2 polynucleotide sequence, ICAM-3 polynucleotide sequence, CD98 polynucleotide sequence, p44 polynucleotide sequence, IFN-p56k polynucleotide sequence, and Staf50 polynucleotide sequence; and
(b) determining whether said non-human nucleotide changes are evolutionarily significant, whereby a polynucleotide sequence of a non-human primate which has been or may be associated with a physiological trait in the non-human primate has undergone evolutionarily significant change relative to humans that exhibits the physiological trait to a lesser degree is identified.
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Abstract
The present invention provides methods for identifying evolutionarily significant polynucleotide and polypeptide sequences in human and/or non-human primates which may be associated with a physiological condition, such as enhanced resistance to AIDS infection. The invention also provides methods for identifying evolutionarily significant polynucleotides with mutations that are correlated with susceptibility to diseases, such as ICAM 1. The methods employ comparison of human and non-human primate sequences using statistical methods. Sequences thus identified may be useful as host therapeutic targets and/or in screening assays.
17 Citations
22 Claims
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1. A method of determining whether a polynucleotide sequence of a non-human primate which has been or may be associated with a physiological trait in the non-human primate has undergone evolutionarily significant change relative to humans that exhibit the physiological trait to a lesser degree, comprising:
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(a) comparing the non-human polynucleotide sequence with the corresponding human primate polynucleotide sequence to identify any nucleotide changes, wherein the polynucleotide sequence is selected from the group consisting of ICAM-1 polynucleotide sequence, ICAM-2 polynucleotide sequence, ICAM-3 polynucleotide sequence, CD98 polynucleotide sequence, p44 polynucleotide sequence, IFN-p56k polynucleotide sequence, and Staf50 polynucleotide sequence; and (b) determining whether said non-human nucleotide changes are evolutionarily significant, whereby a polynucleotide sequence of a non-human primate which has been or may be associated with a physiological trait in the non-human primate has undergone evolutionarily significant change relative to humans that exhibits the physiological trait to a lesser degree is identified. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22)
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18. A method of correlating a polynucleotide sequence of a non-human primate with greater resistance to progression of an infectious disease relative to humans, comprising:
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(a) identifying a human polynucleotide sequence, wherein the expression is modulated upon infection of a human cell with an infectious agent that causes the infectious disease; (b) comparing the human polynucleotide sequences of (a) with a corresponding polynucleotide sequence of a non-human primate that exhibits greater resistance to progression of disease caused by the infectious agent to identify any nucleotide changes; and (c) determining whether said non-human primate nucleotide changes are evolutionarily significant, whereby the polynucleotide sequence of the non-human primate is correlated with greater resistance to progression of an infectious disease relative to humans.
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Specification