Method of haplotype-based genetic analysis for determining risk for developing insulin resistance, coronary artery disease and other phenotypes
Disclosed is a method for determining haplotypes useful for large-scale genetic analysis, within a genomic reference sequence of interest, for a human subpopulation. The method can applied to statistically evaluating the genotypes of subjects for any statistically significant association with a phenotype of interest, such as insulin resistance or coronary artery disease. Thus, also disclosed are a method of detecting a genetic predisposition in a human subject for certain biological conditions, which may be related to coronary artery disease.
1. A method of determining that a human subject has a genetic predisposition for a biological condition, said method comprising:
a) obtaining a biological sample from said subject, said sample containing nucleic acids from said subject; and
b) detecting in said nucleic acids haplotype 12-1 in the lipoprotein lipase (LPL) gene, said haplotype 12-1 comprising:
i) a T at the position corresponding to position 8393 of SEQ ID NO: 25;
ii) a C at the position corresponding to position 9040 of SEQ ID NO: 25;
iii) SEQ ID NO: 60, or the complement thereof, in exon 10 of the LPL gene;
iv) SEQ ID NO: 64, or the complement thereof, in exon 10 of the LPL gene;
v) SEQ ID NO: 68, or the complement thereof, m exon 10 of the LPL gene;
vi) SEQ ID NO: 70, or the complement thereof, m exon 10 of the LPL gene;
vii) SEQ ID NO: 72, or the complement thereof, m exon 10 of the LPL gene;
viii) SEQ ID NO: 74, or the complement thereof, m exon 10 of the LPL gene;
ix) SEQ ID NO: 78, or the complement thereof, m exon 10 of the LPL gene;
x) SEQ ID NO: 80, or the complement thereof, m exon 10 of the LPL gene;
xi) SEQ ID NO: 82, or the complement thereof, in exon 10 of the LPL gene; and
xii) SEQ ID NO: 84, or the complement thereof; in exon 10 of the LPL gene;
wherein said biological condition is a decreased risk of graft worsening and/or graft occlusion of a coronary artery bypass graft (CABG) and/or a decreased diastolic blood pressure (DBP).
2. A method of determining that a human subject has a genetic predisposition for a biological condition, said method comprising:
a) obtaining a biological sample from said subject, said sample containing nucleic acids from said subject; and
b) detecting in said nucleic acids haplotype 12-2 in the lipoprotein lipase (LPL) gene, said haplotype 12-2 comprising:
i) a T at the position corresponding to position 8393 of SEQ ID NO.: 25;
ii) a C at the position corresponding to position 9040 of SEQ ID NO: 25;
iii) SEQ ID NO: 60, or the complement thereof, in exon 10 of the LPL gene;
iv) SEQ ID NO: 64, or the complement thereof, in exon 10 of the LPL gene;
v) SEQ ID NO: 68, or the complement thereof, in exon 10 of the LPL gene;
vi) SEQ ID NO: 70, or the complement thereof, in exon 10 of the LPL gene;
vii) SEQ ID NO: 72, or the complement thereof, in exon 10 of the LPL gene;
viii) SEQ ID NO: 75, or the complement thereof, in exon 10 of the LPL gene
ix) SEQ ID NO: 78, or the complement thereof, in exon 10 of the LPL gene;
x) SEQ ID NO: 80, or the complement thereof; in exon 10 of the LPL gene;
xi) SEQ ID NO: 82, or the complement thereof, in exon 10 of the LPL gene; and
xii) SEQ ID NO: 84, or the complement thereof, in exon 10 of the LPL gene;
wherein said biological condition is a decreased level of high-density lipoprotein cholesterol (HDL-C) and/or a decreased amount of triglyceride (TG) reduction in response to lovastatin therapy.
3. A method of determining that a human subject has a genetic predisposition for a biological condition, said method comprising:
a) obtaining a biological sample from said subject, said sample containing nucleic acids from said subject; and
b) detecting in said nucleic acids haplotype 12-4 in the lipoprotein lipase (LPL) gone, said haplotype 12-4 comprising:
i) a G at the position corresponding to position 8393 of SEQ ID NO: 25;
ii) a G at the position corresponding to position 9040 of SEQ ID NO: 25;
iii) SEQ ID NO: 61, or the complement thereof, in exon 10 of the LPL gone;
iv) SEQ ID NO: 64, or the complement thereof, in exon 10 of the LPL gene;
v) SEQ ID NO: 69, or the complement thereof, in exon 10 of the LPL gene;
vi) SEQ ID NO: 70, or the complement thereof in exon 10 of the LPL gene;
vii) SEQ ID NO: 73, or the complement thereof; in exon 10 of the LPL gene;
viii) SEQ ID NO: 74, or the complement thereof, in exon 10 of the LPL gene;
ix) SEQ ID NO: 79, or the complement thereof, in exon 10 of the LPL gene;
x) SEQ ID NO: 81, or the complement thereof, in exon 10 of the LPL gene;
xi) SEQ ID NO: 83, or the complement thereof, in exon 10 of the LPL gene; and
xii) SEQ ID NO: 84, or the complement thereof, in exon 10 of the LPL gene;
wherein said biological condition is an increased diastolic blood pressure (DBP), an increased high-density lipoprotein cholesterol (HDL-C), and/or a decreased amount of HDL-C reduction in response to lovastatin therapy.