Supplementary Table 1: Primer Sequence Along with Restriction Site for Cloning of BAT1

Supplementary Table 1: Primer sequence along with restriction site for cloning of BAT1, LTA, TNF and BTNL2-DRA interval SNPs

BAT1 Promoter / Restriction site
Forward / 5’ATAT-GCTAGC-CCTTCTATGACACCATTC3’ / Nhe1
Reverse / 5’ATAT-AGATCT-ACAGGGAGAGCGCGTATG3’ / Bgl2
LTA13kb upsyream
Forward / 5’ATAT-GCTAGC-TTCCATTGCTGTGGTTTTCA3’ / Nhe1
Reverse / 5’ATAT-AGATCT-CAGTTGCCCAAGAACAGACA3’ / Bgl2
LTA promoter
Forward / 5’ATAT-GCTAGC-TTGAGGTGACAAGTTGGTATTATCTC3’ / Nhe1
Reverse / 5’ATAT-AGATCT-AGGAGAGCCTCACCTGCTG3’ / Bgl2
TNF-LTB downstream
Forward / 5’ATAT-GGATCC-AAGCCCAGGAGTTTGAGGTT3’ / BamH1
Reverse / 5’ATAT-GTCGAC-TGTCTCCTACCCGACAGTCA3’ / Sal1
rs3136365 at BTNL2-DRA interval
Forward / 5’ATAT-GCTAGC-GGAAAATGAAGGTGGTCCAG3’ / Nhe1
Reverse / 5’ATAT-AGATCT-TGAAGCCACCTGAGAAGGAG3’ / Bgl2
rs7773756 at BTNL2-DRA interval
Forward / 5’ATAT-GCTAGC-GATGGAAGCAGAAGCCAATC3’ / Nhe1
Reverse / 5’ATAT-AGATCT-GACCAAAGGGTGGTCAGAGA3’ / Bgl2

Supplementary Table 2: Characteristics of 111 SNPs used in primary scan of selected genes within 6p21.3 string in Indian samples using MassArray technique*.

Allele / Chr: / Position / Controls (Cohort 1) / Controls (Cohort 2)
S.N. / SNPs / (Major) / (Minor) / (Build 37.1) / GENE / HWE / Minor / HWE / Minor
1 / rs2844518 / C / T / 6 / 31372569 / MICA / 0.000 / 16.05 / 0.000 / 15.48
2 / rs2256183 / A / G / 6 / 31380529 / MICA / 0.23694 / 17.92 / 0.53554 / 18.13
3 / rs2844498 / T / C / 6 / 31476854 / MICB / 0.66114 / 47.11 / 0.33193 / 46.23
4 / rs2259435 / A / G / 6 / 31496915 / BAT1(mccd1-ns) / 0.02244 / 29.64 / 0.13677 / 29.62
5 / rs11796 / T / A / 6 / 31501212 / BAT1 / 0.87608 / 25.23 / 0.99645 / 24.53
6 / rs3130059 / C / G / 6 / 31509284 / BAT1 / 0.72322 / 26.03 / 0.9416 / 25.33
7 / rs2523504 / C / T / 6 / 31510858 / Bat1 Promotor / 0.83488 / 22.04 / 0.66643 / 22.79
8 / rs2251824 / C / T / 6 / 31511857 / ATP6V1G2 downstream / 0.02494 / 28.96 / 0.40556 / 29.51
9 / rs2523503 / C / A / 6 / 31513559 / ATP6V1G2 / 0.02171 / 29.26 / 0.50075 / 29.74
10 / rs2071592 / T / A / 6 / 31515340 / NFKBIL1 Promotor / 0.85331 / 25.2 / 0.60551 / 25.07
11 / rs2071591 / G / A / 6 / 31515799 / NFKBIL1 / 0.81388 / 26.14 / 0.87345 / 25.25
12 / rs2230365 / C / T / 6 / 31525448 / NFKBIL / 0.13892 / 21.18 / 0.15251 / 20.58
13 / rs13192469 / T / C / 6 / 31526856 / LTA Promotor / 0.96772 / 13.55 / 0.55064 / 13.89
14 / rs2009658 / C / G / 6 / 31538244 / LTA Promotor / 0.03592 / 28.92 / 0.87765 / 29.36
15 / rs3093539 / G / A / 6 / 31538277 / LTA Promotor / Homo / 0
16 / rs34166208 / A / 6 / 31538297 / LTA Promotor / Homo / 0
17 / rs36221459 / GTTT / DEL / 6 / 31538422 / LTA Promotor / 0.07479 / 1.71 / 0.56872 / 1.99
18 / rs4647189 / AAAC / DEL / 6 / 31538429 / LTA Promotor / NW / NW
19 / rs36221456 / T / A / 6 / 31538863 / LTA Promotor / NW / NW
20 / rs36221311 / C / G / 6 / 31539602 / LTA Promotor / 0.98485 / 0.07
21 / rs3093541 / AG / 6 / 31539645 / LTA Promotor / Homo / 0
22 / rs36221310 / C / A / 6 / 31539649 / LTA Promotor / 0.97004 / 0.14
23 / rs2844482(-294) / C / T / 6 / 31539767 / LTA Promotor / 0.47191 / 29.03 / 0.14955 / 29.22
24 / rs2071590(-293) / G / A / 6 / 31539768 / LTA Promotor / 0.10775 / 23.4 / 0.09236 / 23.74
25 / rs36221306 / C / T / 6 / 31539999 / LTA Promotor / 0.98487 / 0.07
26 / rs1800683(+10) / G / A / 6 / 31540071 / LTA / 0.35048 / 25.82 / 0.32912 / 25.17
27 / rs2239704(+80) / C / A / 6 / 31540141 / LTA / 0.21178 / 39.23 / 0.01419 / 39.34
28 / rs34880415 / T / A / 6 / 31540620 / LTA / 0.98492 / 0.07
29 / rs3093542 / G / C / 6 / 31540693 / LTA / 0.988 / 0.6 / 0.85191 / 0.49
30 / rs2229092 / A / C / 6 / 31540757 / LTA / 0.62038 / 4.55 / 0.95496 / 3.7
31 / rs1041981 / C / A / 6 / 31540784 / LTA / 0.81982 / 24.57 / 0.93486 / 24.37
32 / rs4647195 / T / C / 6 / 31540957 / LTA / Homo / 0
33 / rs4647196 / C / 6 / 31541032 / LTA / Homo / 0
34 / rs3093544 / A / G / 6 / 31541779 / LTA / 0.96983 / 0.14
35 / rs4645834 / G / 6 / 31541839 / LTA / Homo / 0
36 / rs17207127 / C / T / 6 / 31541948 / LTA / 0.96529 / 0.2
37 / rs3093545 / G / C / 6 / 31541959 / LTA / 0.75988 / 1.14 / 0.63351 / 1.23
38 / rs17207134 / T / C / 6 / 31542113 / LTA downstream / 0.000 / 0.29
39 / rs4248157 / C / T / 6 / 31542143 / LTA downstream / 0.9697 / 0.14
40 / rs9282875 / C / 6 / 31542266 / LTA downstream / Homo / 0
41 / rs1799964 / T / C / 6 / 31542308 / LTA downstream / 0.53879 / 36.66 / 0.20029 / 36.89
42 / rs4647198 / C / 6 / 31542335 / LTA downstream / Homo / 0
43 / rs9282876 / T / 6 / 31542362 / LTA downstream / Homo / 0
44 / rs2507961 / G / 6 / 31542454 / LTA downstream / Homo / 0
45 / rs4248158 / C / T / 6 / 31542533 / TNF Promotor / 0.78173 / 12.41 / 0.52263 / 13.07
46 / rs4248159 / C / A / 6 / 31542580 / TNF Promotor / 0.98489 / 0.07
47 / rs2857712 / A / 6 / 31542653 / TNF Promotor / Homo / 0
48 / rs2736196 / C / A / 6 / 31542655 / TNF Promotor / 0.98484 / 0.07
49 / rs2736195 / A / 6 / 31542691 / TNF Promotor / Homo / 0
50 / rs1800195 / G / 6 / 31542764 / TNF Promotor / Homo / 0
51 / rs4248163 / C / G / 6 / 31542828 / TNF Promotor / 0.93927 / 0.29
52 / rs1800750 / G / A / 6 / 31542963 / TNF Promotor / 0.90773 / 0.44
53 / rs1800629 / G / A / 6 / 31543031 / TNF / 0.03 / 7.56 / 0.86518 / 7.17
54 / rs4987027 / C / 6 / 31543094 / TNF / Homo / 0
55 / rs361525 / G / A / 6 / 31543101 / TNF / 0.96479 / 5.42 / 0.92108 / 5.34
56 / rs4647199 / AG / 6 / 31543383 / TNF / Homo / 0
57 / rs3093660 / C / G / 6 / 31543406 / TNF / Homo / 0
58 / rs2515924 / C / 6 / 31543491 / TNF / Homo / 0
59 / rs2228088 / G / 6 / 31543605 / TNF / Homo / 0
60 / rs3179060 / C / 6 / 31543672 / TNF / Homo / 0
61 / rs1800610 / G / A / 6 / 31543827 / TNF / 0.24096 / 13.41 / 0.78628 / 13.49
62 / rs4645842 / DEL / AG / 6 / 31544069 / TNF / 0.00103 / 1.07 / 0.00908 / 0.9
63 / rs3093662 / A / G / 6 / 31544189 / TNF / 0.38394 / 5.63 / 0.33679 / 5.85
64 / rs3093663 / T / 6 / 31544225 / TNF / Homo / 0
65 / rs35131721 / C / 6 / 31544315 / TNF / Homo / 0
66 / rs3730322 / G / 6 / 31544418 / TNF / Homo / 0
67 / rs1800619 / T / 6 / 31544506 / TNF / Homo / 0
68 / rs4645843 / C / T / 6 / 31544562 / TNF / 0.87618 / 0.6
69 / rs1800620 / G / A / 6 / 31544591 / TNF / 0.000 / 0.29
70 / rs4645844 / G / 6 / 31544652 / TNF / Homo / 0
71 / rs13306710 / G / A / 6 / 31544695 / TNF / 0.000 / 0.36
72 / rs28646872 / T / G / 6 / 31544771 / TNF / 0.98478 / 0.07
73 / rs1800618 / C / 6 / 31544918 / TNF / Homo / 0
74 / rs11574936 / T / 6 / 31545193 / TNF / Homo / 0
75 / rs3093665 / A / C / 6 / 31545391 / TNF / 0.81829 / 0.86
76 / rs10947218 / T / C / 6 / 31545631 / TNF / Homo / 0
77 / rs3093666 / C / T / 6 / 31545733 / TNF downstream / NW / NW
78 / rs3093667 / G / 6 / 31545767 / TNF downstream / Homo / 0
79 / rs36052314 / C / 6 / 31546728 / TNF downstream / Homo / 0
80 / rs3093670 / G / 6 / 31546954 / TNF downstream / Homo / 0
81 / rs3093671 / G / A / 6 / 31546980 / TNF downstream / 0.06397 / 21.9 / 0.47606 / 22.93
82 / rs3093672 / C / T / 6 / 31547420 / TNF downstream / 0.94728 / 3.68 / 0.6543 / 3.3
83 / rs3093561 / G / A / 6 / 31547474 / TNF downstream / 0.000 / 2.28 / 0.000 / 1.08
84 / rs769178 / G / T / 6 / 31547514 / TNF downstream / 0.30529 / 14.84 / 0.81214 / 14.82
85 / rs769177 / C / T / 6 / 31547611 / TNF downstream / 0.074 / 7.36 / 0.03818 / 7.64
86 / rs769176 / C / T / 6 / 31547689 / LTB downstream / 0.89431 / 0.5 / 0.82234 / 0.59
87 / rs3093559 / C / T / 6 / 31547792 / LTB downstream / 0.80539 / 0.92 / 0.76365 / 1.04
88 / rs3093558 / C / T / 6 / 31547819 / LTB downstream / Homo / 0
89 / rs3093557 / G / 6 / 31548196 / LTB downstream / Homo / 0
90 / rs4645846 / G / C / 6 / 31548266 / LTB downstream / 0.96963 / 0.14
91 / rs769175 / T / 6 / 31548368 / LTB / Homo / 0
92 / rs3093556 / A / G / 6 / 31548451 / LTB / 0.43491 / 5.42 / 0.70091 / 4.22
93 / rs4248165 / G / 6 / 31548528 / LTB / Homo / 0
94 / rs2229699 / G / T / 6 / 31548856 / LTB / 0.96733 / 0.17
95 / rs2229698 / C / 6 / 31548870 / LTB / Homo / 0
96 / rs3093555 / C / G / 6 / 31548890 / LTB / 0.000 / 0.35
97 / rs11574937 / T / 6 / 31549069 / LTB / Homo / 0
98 / rs4647188 / C / A / 6 / 31549285 / LTB / 0.98479 / 0.07
99 / rs4647186 / G / C / 6 / 31549364 / LTB / 0.9848 / 0.07
100 / rs3093554 / C / 6 / 31549407 / LTB / Homo / 0
101 / rs3093553 / T / G / 6 / 31549556 / LTB / 0.53038 / 6.56 / 0.61452 / 7.05
102 / rs4647184 / T / 6 / 31549666 / LTB / Homo / 0
103 / rs4647181 / C / 6 / 31549753 / LTB / Homo / 0
104 / rs41273244 / C / 6 / 31549755 / LTB / Homo / 0
105 / rs4647180 / C / 6 / 31549777 / LTB / Homo / 0
106 / rs11548257 / A / 6 / 31549967 / LTB / Homo / 0
107 / rs4647178 / A / 6 / 31549998 / LTB / Homo / 0
108 / rs4647177 / T / G / 6 / 31550254 / LTB promotor / Homo / 0
109 / rs3135365 / A / C / 6 / 32497233 / HLA classII BTNL2-DRA / 0.48876 / 20.68 / 0.47764 / 22.47
110 / rs7773756 / C / T / 6 / 32510442 / HLA classII BTNL2-DRA / 0.85516 / 42.87 / 0.75334 / 45.31
111 / rs7744001 / G / A / 6 / 32734064 / HLA classII BTNL2-DRA / 0.01786 / 42.7 / 0.19597 / 43.79

*In addition 120 SNPs in HLA-A, -B,-C genes (HLA class I) and class II (HLA-DRB1) were typed using commercially available allele specific PCR kit + six more SNPs within BTNL2 gene genotyped by sequencing. NW: SNPs not worked.

Supplementary Table 3: Frequencies of HLA-A,-B,-C (class I) and DRB1 (class II) alleles and their pairwise LD (r2) values with nine significant SNPs.

HLA alleles / Frequency / rs2523504 / rs2230365 / rs13192469 / rs36221459 / rs1800629 / rs1800610 / rs769178 / rs3135365 / rs7773756
HLA-DRB1*01 / 0.033
HLA-DRB1*03 / 0.057 / 0.016 / 0.019 / 0.011 / 0.002 / 0.391 / 0.011 / 0.011 / 0.03 / 0.088
HLA-DRB1*04 / 0.098 / 0.002 / 0 / 0.02 / 0.004 / 0 / 0 / 0 / 0.053 / 0.107
HLA-DRB1*07 / 0.098 / 0.014 / 0.034 / 0.001 / 0.001 / 0.002 / 0.019 / 0.02 / 0.053 / 0.031
HLA-DRB1*10 / 0.066 / 0.051 / 0.077 / 0.095 / 0.01 / 0.006 / 0.012 / 0.004 / 0.034 / 0.049
HLA-DRB1*11 / 0.041
HLA-DRB1*12 / 0.008
HLA-DRB1*13 / 0.074 / 0.021 / 0.025 / 0.01 / 0.003 / 0.079 / 0.009 / 0.007 / 0.039 / 0.016
HLA-DRB1*14 / 0.057 / 0.016 / 0.008 / 0.011 / 0.002 / 0.007 / 0 / 0.001 / 0.013 / 0.088
HLA-DRB1*15 / 0.311 / 0.002 / 0.006 / 0.005 / 0.007 / 0.002 / 0 / 0 / 0.556 / 0.163
HLA-DRB1*16 / 0.008
HLA-A*01 / 0.136 / 0.024 / 0.059 / 0.019 / 0.004 / 0.018 / 0 / 0 / 0.009 / 0
HLA-A*02 / 0.127 / 0.016 / 0.022 / 0.006 / 0.002 / 0.016 / 0.003 / 0.003 / 0.124 / 0.069
HLA-A*03 / 0.027
HLA-A*11 / 0.173 / 0.003 / 0.013 / 0.028 / 0.01 / 0.002 / 0.01 / 0.01 / 0.001 / 0.006
HLA-A*23 / 0.009
HLA-A*24 / 0.155 / 0.027 / 0.006 / 0.015 / 0.005 / 0.02 / 0.031 / 0.031 / 0.054 / 0.075
HLA-A*26 / 0.009
HLA-A*30 / 0.045
HLA-A*31 / 0.009
HLA-A*32 / 0.036
HLA-A*33 / 0.108 / 0.013 / 0.018 / 0.009 / 0.006 / 0.114 / 0 / 0 / 0.033 / 0.034
HLA-A*66 / 0.045
HLA-A*68 / 0.109 / 0.001 / 0.004 / 0 / 0.004 / 0.014 / 0.028 / 0.028 / 0.005 / 0.005
HLA-B*07 / 0.043
HLA-B*13 / 0.074 / 0.017 / 0.001 / 0.016 / 0.009 / 0.007 / 0.09 / 0.09 / 0.045 / 0.055
HLA-B*15 / 0.085 / 0.052 / 0.043 / 0.094 / 0.478 / 0.009 / 0.002 / 0.002 / 0.054 / 0.002
HLA-B*18 / 0.032
HLA-B*27 / 0.096 / 0.001 / 0.001 / 0.011 / 0.002 / 0.065 / 0.019 / 0.019 / 0.006 / 0.01
HLA-B*35 / 0.053 / 0.012 / 0.007 / 0.012 / 0.002 / 0.005 / 0.008 / 0.008 / 0.038 / 0
HLA-B*37 / 0.032
HLA-B*39 / 0.011
HLA-B*40 / 0.17 / 0.008 / 0 / 0.009 / 0.009 / 0.019 / 0 / 0 / 0.069 / 0
HLA-B*41 / 0.011
HLA-B*44 / 0.085 / 0.032 / 0.032 / 0.019 / 0.005 / 0.011 / 0.016 / 0.016 / 0.002 / 0.058
HLA-B*47 / 0.011
HLA-B*49 / 0.011
HLA-B*51 / 0.085 / 0.032 / 0.032 / 0.021 / 0.004 / 0.004 / 0.019 / 0.019 / 0.013 / 0.002
HLA-B*52 / 0.085 / 0 / 0.006 / 0.008 / 0.004 / 0.004 / 0.003 / 0.003 / 0.002 / 0.025
HLA-B*54 / 0.011
HLA-B*55 / 0.032
HLA-B*57 / 0.032
HLA-B*58 / 0.043
HLA-Cw1 / 0.034
HLA-Cw10 / 0.06 / 0.011 / 0 / 0.011 / 0.002 / 0.431 / 0.009 / 0.009 / 0 / 0.026
HLA-Cw2 / 0.043
HLA-Cw3 / 0.017
HLA-Cw4 / 0.121 / 0.001 / 0.017 / 0.001 / 0.006 / 0.012 / 0 / 0 / 0.008 / 0.002
HLA-Cw5 / 0.026
HLA-Cw6 / 0.121 / 0.046 / 0.019 / 0.033 / 0.001 / 0.012 / 0 / 0 / 0.026 / 0.003
HLA-Cw7 / 0.121 / 0.026 / 0.035 / 0.002 / 0.016 / 0 / 0.003 / 0.003 / 0.018 / 0.081
HLA-Cw8 / 0.44 / 0.049 / 0.027 / 0.032 / 0.004 / 0.016 / 0.003 / 0.003 / 0.036 / 0.014
HLA-Cw9 / 0.017

Supplementary Table 4: Pairwise LD values (D' and r2) between BTNL2-DRA interval SNPs (rs7773756, rs3135365) and six BTNL2 gene SNPs (located within promoter, intron1 and intron 3) in four HapMap and presently studied North Indian populations.

YRI
BTNL2 Promoter / BTNL2 intron1 / BTNL2 inton3
rs3763309 / rs3763312 / rs3793127 / rs3117116 / rs2294884 / rs4248166
rs7773756 / D' / 0.743 / 0.739 / 0.743 / 0.209 / 0.873 / 0.754
r2 / 0.089 / 0.087 / 0.089 / 0.003 / 0.068 / 0.053
rs3135365 / D' / 0.747 / 0.73 / 0.747 / 0.89 / 1 / 1
r2 / 0.023 / 0.021 / 0.023 / 0.193 / 0.077 / 0.08
CEU
rs7773756 / D' / 1 / 0.978 / 1 / 1 / 0.815 / 0.812
r2 / 0.524 / 0.508 / 0.524 / 0.158 / 0.077 / 0.077
rs3135365 / D' / 1 / 0.933 / 1 / 1 / 1 / 1
r2 / 0.136 / 0.121 / 0.136 / 0.608 / 0.065 / 0.065
CHB
rs7773756 / D' / 1 / 1 / 1 / 1 / 0.396 / 0.405
r2 / 0.082 / 0.082 / 0.082 / 0.21 / 0.067 / 0.071
rs3135365 / D' / 1 / 1 / 1 / 0.399 / 1 / 1
r2 / 0.016 / 0.016 / 0.016 / 0.151 / 0.041 / 0.04
JPT
rs7773756 / D' / 1 / 1 / 1 / 1 / 0.184 / 0.168
r2 / 0.176 / 0.176 / 0.176 / 0.177 / 0.007 / 0.005
rs3135365 / D' / 1 / 1 / 1 / 0.542 / 1 / 1
r2 / 0.028 / 0.028 / 0.028 / 0.264 / 0.076 / 0.079
North Indian population
rs7773756 / D' / 0.937 / 0.918 / 0.73 / 1 / 0.549 / 0.907
r2 / 0.255 / .213 / 0.18 / 0.023 / 0.048 / 0.096
rs3135365 / D' / 0.757 / O.874 / 1 / 1 / 0.805 / 1
r2 / 0.066 / 0.095 / 0.134 / 0.063 / 0.037 / 0.043