- Email: [email protected]
HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies for a Hong Kong Chinese population of 1064 individuals
Human Immunology xxx (xxxx) xxx–xxx
Contents lists available at ScienceDirect
Human Immunology journal homepage: www.elsevier.com/locate/humimm
HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies for a Hong Kong Chinese population of 1064 individuals Janette Kwoka, , W.H. Tanga, W.K. Chua, Zhongyi Liub, Wanling Yangb, C.K. Leec, Derek Middletond ⁎
a
Division of Transplantation and Immunogenetics, Department of Pathology, Queen Mary Hospital, Hong Kong Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong c Hong Kong Red Cross Blood Transfusion Services, Hong Kong, China d Transplant Immunology, Royal Liverpool Hospital, Liverpool, UK b
ABSTRACT
HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies have been calculated from 1064 southern Chinese unrelated donors in a Hong Kong Bone Marrow Donor Registry. This is the first paper to report the distribution of DQB1-DQA1 and DPB1-DPA1 alleles in Hong Kong Chinese. Due to the HardyWeinberg equilibrium proportions (HWEP) deviation in DPB1 loci, this information may be of limited use for phylogenetic, comparative studies but will be useful for the permissible matching in HLA-DPB1 for Chinese patients awaiting haematopoietic stem cell transplantation in the near future due to the new recommendation of NMDP matching guidelines. The allele and haplotype data are available in the Allele Frequencies Net Database under the population name ‘‘Hong Kong Chinese HKBMDR, DQ and DP’’ and the identifier (AFND3667).
This paper reports the HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies of a predominantly southern Chinese registry in Hong Kong operated by the Hong Kong Bone Marrow Donor Registry (HKBMDR) under the Hong Kong Red Cross Blood Transfusion Service. Informed consent was obtained for the registration as unrelated haematopoietic stem cell donors. Hong Kong has a predominantly Chinese population and a history as a British colony. At the beginning of the British rule from the midnineteenth century, Hong Kong was a small fishing community and a haven for travelers and pirates in the South China Sea. Hong Kong served as a refuge for exiles from mainland China following the establishment of the Chinese Republic in 1912. Hong Kong's population increased dramatically after the war, as a wave of skilled migrants from mainland China moved in to seek refuge from the Chinese Civil War. When the Communist Party established the People’s Republic of China in 1949, hundreds of thousands of people fled to Hong Kong [1]. Since the 1997 Handover, an increase in immigrants from mainland China has brought an increasing number of mainlanders to Hong Kong [2]. Hong Kong is located to the south of mainland China and had a population of around 7.49 million at the end of 2018 [3]. The current population of Hong Kong comprises 92% ethnic Chinese [4]. A major part of Hong Kong's residents originated from the neighbouring Guangdong province in Southern China [5]. About 92% of the people of
Hong Kong are of Chinese descent [4,6], the majority of whom are Taishanese, Chiu Chow, other Cantonese people, and Hakka. Hong Kong's Han majority originate mainly from the Guangzhou and Taishan regions in Guangdong province [5]. The remaining 8% of the population is composed of non-ethnic Chinese [6]. Chinese and English are the official languages of Hong Kong. Cantonese speakers account for 89.5% of population [4,7]. English being an official language accounts 3.1% of the population as an everyday language and by 34.9% as a second language [8]. The HKBMDR was established in 2005, and manages the unrelated donor registry database previously managed by the Hong Kong Marrow Match Foundation. The HKBMDR continues to recruit donors from the Hong Kong community, primarily through blood donation drives. Therefore, the HKBMDR database consists predominantly of Chinese donors living in Hong Kong. HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotype was performed using Next Generation Sequencing (AllType NGS; One Lambda, Canoga park, California) on the Illumina MiSeq system platform, from exons 2 to 3′UTR for DQB1 and DPB1 loci and full gene for DQA1 and DPA1 loci. The reads were analyzed using the TypeStream Visual Software version 1.3.0 (One Lambda). All typing was performed at the Division of Transplantation and Immunogenetics, Queen Mary Hospital in Hong Kong. Alleles were determined according to IMGT/HLA Database
⁎ Corresponding author at: Division of Transplantation and Immunogenetics, Department of Pathology, Queen Mary Hospital, Pokfulam Road, Hong Kong Special Administrative Region. E-mail address: [email protected] (J. Kwok).
https://doi.org/10.1016/j.humimm.2019.11.005 Received 12 September 2019; Received in revised form 7 November 2019; Accepted 7 November 2019 0198-8859/ © 2019 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Please cite this article as: Janette Kwok, et al., Human Immunology, https://doi.org/10.1016/j.humimm.2019.11.005
Human Immunology xxx (xxxx) xxx–xxx
J. Kwok, et al.
Table 1 Genotype, observed and expected number in DPB1 loci for 2n = 2128 (p < 0.05). Genotype
Observed/expected
Chen's P value
Diff P value
HLA-DPB1* 02:02 + 14:01 03:01 + 104:01 01:01 + 01:01 03:01 + 834:01 16:01 + 135:01 17:01 + 31:01 02:01 + 09:01 09:01 + 26:01 31:01 + 41:01 04:02 + 744:01 04:01 + 10:01 04:01 + 41:01 05:01 + 105:01
(11/4.131109) (4/0.558271) (2/0.067904) (1/0.046523) (1/0.023496) (2/0.116541) (8/3.679511) (1/0.012688) (1/0.022556) (1/0.042293) (1/0.068609) (2/0.411654) (3/1.256109)
< 0.0001 < 0.0001 0.0061 0.0038 0.0050 0.0099 0.0156 0.0172 0.0216 0.0234 0.0291 0.0438 0.0448
< 0.0001 0.0040 0.0061 0.0339 0.0116 0.0101 0.0161 0.0200 0.0235 0.0411 0.0733 0.0771 0.0448
Table 3a Ambiguities cannot be resolved in DPB1 locus due to phasing issue in 1064 samples. HLA-DPB1*
Ambiguities
N (Frequency in percentage)
02:02 + 14:01 03:01 + 04:02 04:01 + 09:01 04:01 + 10:01 04:01 + 135:01 04:02 + 02:01 04:02 + 02:02 04:02 + 04:01 04:02 + 744:01
547:01 + 651:01 351:01 + 463:01 350:01 + 899:01 350:01 + 902:01 350:01 + 744:01 105:01 + 416:01 105:01 + 721:01 105:01 + 126:01 105:01 + 790:01
11 (1.03%) 3 (0.28%) 3 (0.28%) 1 (0.09%) 2 (0.19%) 3 (0.28%) 5 (0.47%) 5 (0.47%) 1 (0.09%)
Table 3b Ambiguities cannot be resolved in DQB1 locus due to exon 1 in 2128 alleles.
release 3.35.0. HLA haplotype frequencies were calculated using the Markov Chain Monte Carlo algorithm PHASE [9]. 495 HLADQB1 ~ DQA1 ~ DPB1 ~ DPA1 haplotypes were estimated from these donors (n = 1064). 1064 Chinese unrelated donors were randomly selected from HKBMDR in the previous cohort tested for A, B, C and DRB1 loci. Allele frequencies for each locus were determined via direct counting. Haplotype frequencies were estimated using the Markov Chain Monte Carlo algorithm PHASE [9]; adherence to HWEP was also assessed using PyPop 0.7.0 [10]. Specific genotypes displaying HWEP deviations at the HLA-DPB1 are shown in Table 1. Observed and expected number of all heterozygotes and all homozygotes in DQB1, DQA1 and DPB1 and DPA1 are shown in Table 2. The HWEP deviation at the HLA-DPB1 locus may be due to the extreme excess of DPB1*02:02 + DPB1*14:01 genotypes (11 observed, 4 expected; p < 0.0001). The excess of DPB1*02:02 + DPB1*14:01 genotypes can be contributed by ambiguity resolution selection with the limitation of phasing since the differences lie in exons 2 and 3. The ambiguities were found in DPB1 and DQB1 loci but not DPA1 or DQA1 and their number and percentages in this cohort are listed in Table 3. The selection is based on those listed in the AFND website for other cities of China and Japan populations and the IMGT HLA website in which most of these ambiguities belong to non-Chinese or unknown origin. The allele and haplotype frequency data are available in the Allele Frequencies Net Database under the population name ‘‘Hong Kong Chinese HKBMDR, DQ and DP’’ and the identifier (AFND3667) [11] and are listed in Supplementary tables. 21 HLA-DQB1, 17 HLA-DQA1, 29 HLA-DPB1 and 6 HLA-DPA1 alleles were found in this cohort. The most common HLA-DQB1, -DQA1, -DPB1, and -DPA1 alleles were DQB1*03:01 (22.89%), DQA1*01:02 (18.61%), DPB1*05:01 (41.87%) and DPA1*02:02 (55.78%) respectively. A total of 46 DQB1 ~ DQA1 haplotypes and 54 DPB1 ~ DPA1 haplotypes were detected. 39 HLA-DQB1 ~ DQA1 haplotypes and 45 HLA-DPB1 ~ DPA1 haplotypes had frequencies of greater than or equal to 0.0235%. The top
HLA-DQB1*
Ambiguities
N (Frequency in percentage)
03:01 03:02
03:297/03:276 N 03:289
203 (9.54%) 134 (6.30%)
three most common DQB1 ~ DQA1 haplotypes were DQB1*03:03 ~ DQA1*03:02 (14.75%), DQB1*03:01 ~ DQA1*06:01 (13.16%) and DQB1*05:02 ~ DQA1*01:02 (8.04%). The top three most common DPB1 ~ DPA1 haplotypes were DPB1*05:01 ~ DPA1*02:02 (40.23%), DPB1*02:01 ~ DPA1*01:03 (11.15%) and DPB1*04:01 ~ DPA1*01:03 (6.81%). A total of 495 HLADQB1 ~ DQA1 ~ DPB1 ~ DPA1 haplotypes were detected and 300 of them had frequencies greater than or equal to 0.0235%. After reviewing data in the Allele Frequencies Net Database, we found our results on HLA-DQB1 and HLA-DPB1 allele frequencies to be quite comparable to those of Han Chinese population with the sample sizes of 264 in China Canton Han and of 86 in China Guangzhou Han populations [11]. The most common DQB1 allele, DQB1*03:01 (22.9%), ranked the first in the China Canton Han (24.2%) and also China Guangzhou Han Chinese (23.3%) [11]. The most common DPB1 allele, DPB1*05:01 (41.87%), also ranked the first in the China Canton Han (36.0%) and the China Guangzhou Han Chinese (51.2%) [11]. However, there were no data for DQA1 and DPA1 for these two Chinese populations. 1. Source(s) of support NIL. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Table 2 Observed and expected number in HLA-DQB1 ~ DQB1, DQA1 ~ DQA1 and DPB1 ~ DPB1 and DPA1 ~ DPA1 (2n = 2128). HLA locus
HLA-DQB1 HLA-DQA1 HLA-DPB1 HLA-DPA1
All homozygotes
All heterozygotes
P value (overall)
Observed
Expected
P value
Observed
Expected
P value
140 136 239 462
130.22 112.56 229.60 433.60
0.3914 0.0271 0.5349 0.1726
924 928 825 602
933.78 951.44 834.40 630.40
0.7489 0.4472 0.7448 0.2580
2
0.8163 0.1393 0.0285 0.3015
Human Immunology xxx (xxxx) xxx–xxx
J. Kwok, et al.
Appendix A. Supplementary data
htm. Retrieved 9 September 2019. [5] Fan Shuh Ching (1974). “The Population of Hong Kong” (PDF). World Population Year (Committee for International Coordination of National Research in Demography): 18-20. Retrieved 9 September 2019. [6] 1 Population Census – Summary Results (PDF) (Report). Census and Statistics Department. February 2. Retrieved 9 September 9. [7] “Hong Kong Demographics Profile 2014”. www.indexmundi.com, Retrieved 19 September 2016. [8] “ICE Hong Kong”. University College London Retrieved 19 September 2016. [9] M. Stephens, N.J. Smith, P. Donnelly, A new statistical method for haplotype reconstruction from population data, Am. J. Hum. Genet. 68 (2001) 978–989. [10] A.K. Lancaster, et al., PyPop update – a software pipeline for large-scale multi-locus population genomics, Tissue Antigens 69 (2007) 192–197. [11] E.J. Dos Santos, A. McCabe, F.F. Gonzalez-Galarza, A.R. Jones, D. Middleton, Allele frequencies net database: improvements for storage of individual genotypes and analysis of existing data, Hum. Immunol. 77 (2016) 238–248.
Supplementary data to this article can be found online at https:// doi.org/10.1016/j.humimm.2019.11.005. References [1] Wiltshire, Trea (1997). Old Hong Kong. Volume II: 1901-1945 (5th ed.). FormAsia Books. P. 148. ISBN 962-7283-13-4. [2] Yum, Cherry (2007). “Which Chinese? Dialect Choice in Philadelphia's Chinatown” (PDF). Haverford College. Retrieved 9 September 2019. [3] Census and Statistics Department. http://www.censtatd.gov.hk/hkstat/sub/so20. jsp. Retrieved 9 September 2019. [4] “GovHK: Hong Kong – the Facts”. http://www.gov.hk/en/about/abouthk/facts.
3
Contents lists available at ScienceDirect
Human Immunology journal homepage: www.elsevier.com/locate/humimm
HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies for a Hong Kong Chinese population of 1064 individuals Janette Kwoka, , W.H. Tanga, W.K. Chua, Zhongyi Liub, Wanling Yangb, C.K. Leec, Derek Middletond ⁎
a
Division of Transplantation and Immunogenetics, Department of Pathology, Queen Mary Hospital, Hong Kong Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong c Hong Kong Red Cross Blood Transfusion Services, Hong Kong, China d Transplant Immunology, Royal Liverpool Hospital, Liverpool, UK b
ABSTRACT
HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies have been calculated from 1064 southern Chinese unrelated donors in a Hong Kong Bone Marrow Donor Registry. This is the first paper to report the distribution of DQB1-DQA1 and DPB1-DPA1 alleles in Hong Kong Chinese. Due to the HardyWeinberg equilibrium proportions (HWEP) deviation in DPB1 loci, this information may be of limited use for phylogenetic, comparative studies but will be useful for the permissible matching in HLA-DPB1 for Chinese patients awaiting haematopoietic stem cell transplantation in the near future due to the new recommendation of NMDP matching guidelines. The allele and haplotype data are available in the Allele Frequencies Net Database under the population name ‘‘Hong Kong Chinese HKBMDR, DQ and DP’’ and the identifier (AFND3667).
This paper reports the HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies of a predominantly southern Chinese registry in Hong Kong operated by the Hong Kong Bone Marrow Donor Registry (HKBMDR) under the Hong Kong Red Cross Blood Transfusion Service. Informed consent was obtained for the registration as unrelated haematopoietic stem cell donors. Hong Kong has a predominantly Chinese population and a history as a British colony. At the beginning of the British rule from the midnineteenth century, Hong Kong was a small fishing community and a haven for travelers and pirates in the South China Sea. Hong Kong served as a refuge for exiles from mainland China following the establishment of the Chinese Republic in 1912. Hong Kong's population increased dramatically after the war, as a wave of skilled migrants from mainland China moved in to seek refuge from the Chinese Civil War. When the Communist Party established the People’s Republic of China in 1949, hundreds of thousands of people fled to Hong Kong [1]. Since the 1997 Handover, an increase in immigrants from mainland China has brought an increasing number of mainlanders to Hong Kong [2]. Hong Kong is located to the south of mainland China and had a population of around 7.49 million at the end of 2018 [3]. The current population of Hong Kong comprises 92% ethnic Chinese [4]. A major part of Hong Kong's residents originated from the neighbouring Guangdong province in Southern China [5]. About 92% of the people of
Hong Kong are of Chinese descent [4,6], the majority of whom are Taishanese, Chiu Chow, other Cantonese people, and Hakka. Hong Kong's Han majority originate mainly from the Guangzhou and Taishan regions in Guangdong province [5]. The remaining 8% of the population is composed of non-ethnic Chinese [6]. Chinese and English are the official languages of Hong Kong. Cantonese speakers account for 89.5% of population [4,7]. English being an official language accounts 3.1% of the population as an everyday language and by 34.9% as a second language [8]. The HKBMDR was established in 2005, and manages the unrelated donor registry database previously managed by the Hong Kong Marrow Match Foundation. The HKBMDR continues to recruit donors from the Hong Kong community, primarily through blood donation drives. Therefore, the HKBMDR database consists predominantly of Chinese donors living in Hong Kong. HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotype was performed using Next Generation Sequencing (AllType NGS; One Lambda, Canoga park, California) on the Illumina MiSeq system platform, from exons 2 to 3′UTR for DQB1 and DPB1 loci and full gene for DQA1 and DPA1 loci. The reads were analyzed using the TypeStream Visual Software version 1.3.0 (One Lambda). All typing was performed at the Division of Transplantation and Immunogenetics, Queen Mary Hospital in Hong Kong. Alleles were determined according to IMGT/HLA Database
⁎ Corresponding author at: Division of Transplantation and Immunogenetics, Department of Pathology, Queen Mary Hospital, Pokfulam Road, Hong Kong Special Administrative Region. E-mail address: [email protected] (J. Kwok).
https://doi.org/10.1016/j.humimm.2019.11.005 Received 12 September 2019; Received in revised form 7 November 2019; Accepted 7 November 2019 0198-8859/ © 2019 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Please cite this article as: Janette Kwok, et al., Human Immunology, https://doi.org/10.1016/j.humimm.2019.11.005
Human Immunology xxx (xxxx) xxx–xxx
J. Kwok, et al.
Table 1 Genotype, observed and expected number in DPB1 loci for 2n = 2128 (p < 0.05). Genotype
Observed/expected
Chen's P value
Diff P value
HLA-DPB1* 02:02 + 14:01 03:01 + 104:01 01:01 + 01:01 03:01 + 834:01 16:01 + 135:01 17:01 + 31:01 02:01 + 09:01 09:01 + 26:01 31:01 + 41:01 04:02 + 744:01 04:01 + 10:01 04:01 + 41:01 05:01 + 105:01
(11/4.131109) (4/0.558271) (2/0.067904) (1/0.046523) (1/0.023496) (2/0.116541) (8/3.679511) (1/0.012688) (1/0.022556) (1/0.042293) (1/0.068609) (2/0.411654) (3/1.256109)
< 0.0001 < 0.0001 0.0061 0.0038 0.0050 0.0099 0.0156 0.0172 0.0216 0.0234 0.0291 0.0438 0.0448
< 0.0001 0.0040 0.0061 0.0339 0.0116 0.0101 0.0161 0.0200 0.0235 0.0411 0.0733 0.0771 0.0448
Table 3a Ambiguities cannot be resolved in DPB1 locus due to phasing issue in 1064 samples. HLA-DPB1*
Ambiguities
N (Frequency in percentage)
02:02 + 14:01 03:01 + 04:02 04:01 + 09:01 04:01 + 10:01 04:01 + 135:01 04:02 + 02:01 04:02 + 02:02 04:02 + 04:01 04:02 + 744:01
547:01 + 651:01 351:01 + 463:01 350:01 + 899:01 350:01 + 902:01 350:01 + 744:01 105:01 + 416:01 105:01 + 721:01 105:01 + 126:01 105:01 + 790:01
11 (1.03%) 3 (0.28%) 3 (0.28%) 1 (0.09%) 2 (0.19%) 3 (0.28%) 5 (0.47%) 5 (0.47%) 1 (0.09%)
Table 3b Ambiguities cannot be resolved in DQB1 locus due to exon 1 in 2128 alleles.
release 3.35.0. HLA haplotype frequencies were calculated using the Markov Chain Monte Carlo algorithm PHASE [9]. 495 HLADQB1 ~ DQA1 ~ DPB1 ~ DPA1 haplotypes were estimated from these donors (n = 1064). 1064 Chinese unrelated donors were randomly selected from HKBMDR in the previous cohort tested for A, B, C and DRB1 loci. Allele frequencies for each locus were determined via direct counting. Haplotype frequencies were estimated using the Markov Chain Monte Carlo algorithm PHASE [9]; adherence to HWEP was also assessed using PyPop 0.7.0 [10]. Specific genotypes displaying HWEP deviations at the HLA-DPB1 are shown in Table 1. Observed and expected number of all heterozygotes and all homozygotes in DQB1, DQA1 and DPB1 and DPA1 are shown in Table 2. The HWEP deviation at the HLA-DPB1 locus may be due to the extreme excess of DPB1*02:02 + DPB1*14:01 genotypes (11 observed, 4 expected; p < 0.0001). The excess of DPB1*02:02 + DPB1*14:01 genotypes can be contributed by ambiguity resolution selection with the limitation of phasing since the differences lie in exons 2 and 3. The ambiguities were found in DPB1 and DQB1 loci but not DPA1 or DQA1 and their number and percentages in this cohort are listed in Table 3. The selection is based on those listed in the AFND website for other cities of China and Japan populations and the IMGT HLA website in which most of these ambiguities belong to non-Chinese or unknown origin. The allele and haplotype frequency data are available in the Allele Frequencies Net Database under the population name ‘‘Hong Kong Chinese HKBMDR, DQ and DP’’ and the identifier (AFND3667) [11] and are listed in Supplementary tables. 21 HLA-DQB1, 17 HLA-DQA1, 29 HLA-DPB1 and 6 HLA-DPA1 alleles were found in this cohort. The most common HLA-DQB1, -DQA1, -DPB1, and -DPA1 alleles were DQB1*03:01 (22.89%), DQA1*01:02 (18.61%), DPB1*05:01 (41.87%) and DPA1*02:02 (55.78%) respectively. A total of 46 DQB1 ~ DQA1 haplotypes and 54 DPB1 ~ DPA1 haplotypes were detected. 39 HLA-DQB1 ~ DQA1 haplotypes and 45 HLA-DPB1 ~ DPA1 haplotypes had frequencies of greater than or equal to 0.0235%. The top
HLA-DQB1*
Ambiguities
N (Frequency in percentage)
03:01 03:02
03:297/03:276 N 03:289
203 (9.54%) 134 (6.30%)
three most common DQB1 ~ DQA1 haplotypes were DQB1*03:03 ~ DQA1*03:02 (14.75%), DQB1*03:01 ~ DQA1*06:01 (13.16%) and DQB1*05:02 ~ DQA1*01:02 (8.04%). The top three most common DPB1 ~ DPA1 haplotypes were DPB1*05:01 ~ DPA1*02:02 (40.23%), DPB1*02:01 ~ DPA1*01:03 (11.15%) and DPB1*04:01 ~ DPA1*01:03 (6.81%). A total of 495 HLADQB1 ~ DQA1 ~ DPB1 ~ DPA1 haplotypes were detected and 300 of them had frequencies greater than or equal to 0.0235%. After reviewing data in the Allele Frequencies Net Database, we found our results on HLA-DQB1 and HLA-DPB1 allele frequencies to be quite comparable to those of Han Chinese population with the sample sizes of 264 in China Canton Han and of 86 in China Guangzhou Han populations [11]. The most common DQB1 allele, DQB1*03:01 (22.9%), ranked the first in the China Canton Han (24.2%) and also China Guangzhou Han Chinese (23.3%) [11]. The most common DPB1 allele, DPB1*05:01 (41.87%), also ranked the first in the China Canton Han (36.0%) and the China Guangzhou Han Chinese (51.2%) [11]. However, there were no data for DQA1 and DPA1 for these two Chinese populations. 1. Source(s) of support NIL. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Table 2 Observed and expected number in HLA-DQB1 ~ DQB1, DQA1 ~ DQA1 and DPB1 ~ DPB1 and DPA1 ~ DPA1 (2n = 2128). HLA locus
HLA-DQB1 HLA-DQA1 HLA-DPB1 HLA-DPA1
All homozygotes
All heterozygotes
P value (overall)
Observed
Expected
P value
Observed
Expected
P value
140 136 239 462
130.22 112.56 229.60 433.60
0.3914 0.0271 0.5349 0.1726
924 928 825 602
933.78 951.44 834.40 630.40
0.7489 0.4472 0.7448 0.2580
2
0.8163 0.1393 0.0285 0.3015
Human Immunology xxx (xxxx) xxx–xxx
J. Kwok, et al.
Appendix A. Supplementary data
htm. Retrieved 9 September 2019. [5] Fan Shuh Ching (1974). “The Population of Hong Kong” (PDF). World Population Year (Committee for International Coordination of National Research in Demography): 18-20. Retrieved 9 September 2019. [6] 1 Population Census – Summary Results (PDF) (Report). Census and Statistics Department. February 2. Retrieved 9 September 9. [7] “Hong Kong Demographics Profile 2014”. www.indexmundi.com, Retrieved 19 September 2016. [8] “ICE Hong Kong”. University College London Retrieved 19 September 2016. [9] M. Stephens, N.J. Smith, P. Donnelly, A new statistical method for haplotype reconstruction from population data, Am. J. Hum. Genet. 68 (2001) 978–989. [10] A.K. Lancaster, et al., PyPop update – a software pipeline for large-scale multi-locus population genomics, Tissue Antigens 69 (2007) 192–197. [11] E.J. Dos Santos, A. McCabe, F.F. Gonzalez-Galarza, A.R. Jones, D. Middleton, Allele frequencies net database: improvements for storage of individual genotypes and analysis of existing data, Hum. Immunol. 77 (2016) 238–248.
Supplementary data to this article can be found online at https:// doi.org/10.1016/j.humimm.2019.11.005. References [1] Wiltshire, Trea (1997). Old Hong Kong. Volume II: 1901-1945 (5th ed.). FormAsia Books. P. 148. ISBN 962-7283-13-4. [2] Yum, Cherry (2007). “Which Chinese? Dialect Choice in Philadelphia's Chinatown” (PDF). Haverford College. Retrieved 9 September 2019. [3] Census and Statistics Department. http://www.censtatd.gov.hk/hkstat/sub/so20. jsp. Retrieved 9 September 2019. [4] “GovHK: Hong Kong – the Facts”. http://www.gov.hk/en/about/abouthk/facts.
3