Population Haplotype Frequencies Research Articles

Together Inbreeding and Reproductive Compensation Favor Lethal t-Haplotypes.

Male mice who are heterozygous for distorting and non-distorting alleles at the t-haplotype transmit the driving t-haplotype around 90% of the time - a drastic departure from Mendelian expectations. This selfish act comes at a cost. The mechanism underlying transmission distortion in this system causes severe sterility in males homozygous for the drive alleles, ultimately preventing its fixation. Curiously, many driving t-haplotypes also induce embryonic lethality in both sexes when homozygous; however, this is neither universal nor a necessity for this distortion mechanism. Charlesworth provided an adaptive explanation for the evolution of lethal t-haplotypes in a population segregating for distorting and non-distorting t alleles - if mothers compensate by replacing dead embryos with new offspring (or by transferring energy to surviving offspring), a recessive lethal can be favored because it effectively allows mothers the opportunity to trade in infertile males for potentially fertile offspring. This model, however, requires near complete reproductive compensation for the invasion of the lethal t-haplotype and produces an equilibrium frequency of lethal drivers well below what is observed in nature. We show that low levels of systemic inbreeding, which we model as brother-sister mating, allow lethal t-haplotypes to invade with much lower levels of reproductive compensation. Furthermore, inbreeding allows these lethal haplotypes to largely displace the ancestral male-sterile haplotypes. Our results show that together inbreeding and reproductive compensation move expected equilibria closer to observed haplotype frequencies in natural populations and occur under lower, potentially more reasonable, parameters.

Genetic polymorphisms of 19 X-STRs in populations of Hubei Han and Guangxi Zhuang and their comparisons with 13 other Chinese populations

Background A prerequisite for applying short tandem repeat (STR) kits is obtaining population allele and/or haplotype frequencies and forensic parameters. Aim Firstly, we aimed to investigate the population data of 19 X-chromosomal STRs (X-STRs) included in the AGCU X19 STR kit in the Han people residing in Hubei Province, Central China, and the Zhuang people residing in the Guangxi Zhuang Autonomous Region of South China. Furthermore, we compared these population data with those for other Chinese populations. Subjects and methods In total, 509 unrelated Han males and 266 unrelated Zhuang males were genotyped using the AGCU X19 STR kit. Allele frequencies, haplotype frequencies, and forensic parameters were computed, and genetic differences among 15 Chinese populations were analysed. Results The 19 X-STRs showed a high power of discrimination and high mean chance of exclusion, whether calculated using allele or haplotype frequencies. Major differences were found between Han and Oroqen, Uyghur, Mongolian, Tibetan, Li, and Yi populations. Aberrant biallelic patterns at DXS10159, DXS10134, and DXS10079 and allelic dropouts at DXS10164 were observed. Conclusion The 19 X-STRs were highly polymorphic in the Hubei Han and Guangxi Zhuang populations, and the AGCU X19 STR kit was shown to be suitable for forensic casework.

Allele and eight-locus haplotype frequencies in population of Belgorod region, Russia

This paper reports the HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1 and –DPB1 alleles and estimated haplotype frequencies in a population of 153 healthy potential blood marrow donors from Belgorod region, Russia. HLA genotyping was performed by next generation sequencing method (NGS). Statistical analysis were performed using Arlequin software packages. There was no deviation from Hardy-Weinberg Equilibrium detected at HLA-A, -B, -DRB1, -DQA1, -DQB1, and -DPA1 loci. Deviation was detected at the HLA-C and DPB1 locus probably due to an excess of C*12:03:01 and DPB1*04:01:01 homozygotes. These genotype data are available in the Allele Frequencies Net Database under the population name, “Russia, Belgorod Region” and the identifier: 3780.

HLA alleles and haplotype frequencies in Iranian population.

HLA genotyping is a prerequisite for selection of suitable donors in the process of bone marrow transplantation. In the current study, the frequencies of HLA-A, -B, -C and -DRB1 alleles and A-B-C-DRB1 haplotypes were assessed in 855 healthy Iranian persons using a low-resolution sequence specific primer (SSP) kit. Frequencies were compared between 11 subpopulations including Armani, Balouch, Bandari, Turk, Turkaman, Arab, Fars, Kurd, Gilaki, Lor and Mazani. In total, 17 HLA-A alleles were detected, one of which (HLA-A*74) was present only among Lors. HLA-A*23 and -A*26 were the most frequent HLA-A alleles among Armanis. HLA-A*23 was also common among Turkamans. HLA-A*11 and -A*26 were most frequent among the Balouch subpopulation. The former allele was also frequent among Bandaris. HLA-A*02 was identified as the most common HLA-A allele among Turk, Arab and Fars subpopulations. HLA-A*30 were strongly enriched among Gilakis. A total of 31 HLA-B alleles were detected across the target population. While all alleles were present among Fars subgroup, Armanis and Turkamans had the lowest degree of diversity among the alleles examined. Moreover, HLA-B*35 and B*49 alleles were strongly enriched among Armanis and Turkamans, respectively. A total of 13 HLA-C alleles were identified across the population, all of which were present in the Fars subpopulation. HLA-C*03 and C*04 were the only HLA-C alleles identified among the Bandari subpopulation. HLA-DRB1*08 was not detected in any subpopulation other than Fars. HLA-DRB1*16 was significantly enriched among Bandaris. These data have practical significance in anthropological studies, disease association investigations and bone marrow transplantation.

Imbalanced segregation of recombinant haplotypes in hybrid populations reveals inter- and intrachromosomal Dobzhansky-Muller incompatibilities.

Dobzhansky-Muller incompatibilities (DMIs) are a major component of reproductive isolation between species. DMIs imply negative epistasis and are exposed when two diverged populations hybridize. Mapping the locations of DMIs has largely relied on classical genetic mapping. Approaches to date are hampered by low power and the challenge of identifying DMI loci on the same chromosome, because strong initial linkage of parental haplotypes weakens statistical tests. Here, we propose new statistics to infer negative epistasis from haplotype frequencies in hybrid populations. When two divergent populations hybridize, the variance in heterozygosity at two loci decreases faster with time at DMI loci than at random pairs of loci. When two populations hybridize at near-even admixture proportions, the deviation of the observed variance from its expectation becomes negative for the DMI pair. This negative deviation enables us to detect intermediate to strong negative epistasis both within and between chromosomes. In practice, the detection window in hybrid populations depends on the demographic scenario, the recombination rate, and the strength of epistasis. When the initial proportion of the two parental populations is uneven, only strong DMIs can be detected with our method unless migration prevents parental haplotypes from being lost. We use the new statistics to infer candidate DMIs from three hybrid populations of swordtail fish. We identify numerous new DMI candidates, some of which are inferred to interact with several loci within and between chromosomes. Moreover, we discuss our results in the context of an expected enrichment in intrachromosomal over interchromosomal DMIs.

HLA-G 3’UTR haplotype frequencies in highland and lowland South Native American populations

Human Leukocyte Antigen (HLA)-G participates in several biological processes, including reproduction, vascular remodeling, immune tolerance, and hypoxia response. HLA-G is a potential candidate gene for high altitude adaptation since its expression is modulated in both micro and macro environment under hypoxia and constant cellular stress. Besides the promoter region, the HLA-G 3′untranslated region (UTR) influences HLA-G expression patterns through several post-transcriptional mechanisms. Currently, the 3′UTR genetic diversity in terms of altitude adaptation of Native American populations is still unexplored, particularly at high altitude ecoregions. Here, we evaluated 288 Native Americans from 9 communities located in the Andes [highland (HL); ≥2,500 m (range = 2,838–4,433 m)] and 8 populations located in lowland (LL) regions [<2,500 m (range = 80–431 m); Amazonian tropical forest, Brazilian central plateau, and Chaco] of South America. In total, nine polymorphic sites and ten haplotypes were observed. The most frequent haplotypes (UTR-1, UTR-2, and UTR-3) accounted for ∼ 77% of haplotypes found in LL, while in the HL, the same haplotypes reach ∼ 93%. Also, a remarkable high frequency of putative ancestral UTR-5 haplotype was observed in LL (21.5%), while in HL UTR-2 reaches up to 47%. Further, UTR-2 frequency positively correlates with altitude-related variables, while a negative correlation for UTR-5 was observed. From an evolutionary perspective, we observed a tendency towards balancing selection in HL and LL populations thus suggesting that haplotypes of ancient and more derived alleles may have been co-opted for relatively recent adaptations such as those experienced by modern humans in the highland and lowland of South America. We also discuss how long-term balancing selection can be a reservoir of genetic variants that can be positively selected. Finally, our study provides some pieces of evidence that HLA-G 3′UTR haplotypes may have contributed to high altitude adaptation in the Andes.

High-resolution HLA allele and haplotype frequencies in several unrelated populations determined by next generation sequencing: 17th International HLA and Immunogenetics Workshop joint report

The primary goal of the unrelated population HLA diversity (UPHD) component of the 17th International HLA and Immunogenetics Workshop was to characterize HLA alleles at maximum allelic-resolution in worldwide populations and re-evaluate patterns of HLA diversity across populations. The UPHD project included HLA genotype and sequence data, generated by various next-generation sequencing methods, from 4,240 individuals collated from 12 different countries. Population data included well-defined large datasets from the USA and smaller samples from Europe, Australia, and Western Asia. Allele and haplotype frequencies varied across populations from distant geographical regions. HLA genetic diversity estimated at 2- and 4-field allelic resolution revealed that diversity at the majority of loci, particularly for European-descent populations, was lower at the 2-field resolution.Several common alleles with identical protein sequences differing only by intronic substitutions were found in distinct haplotypes, revealing a more detailed characterization of linkage between variants within the HLA region. The examination of coding and non-coding nucleotide variation revealed many examples in which almost complete biunivocal relations between common alleles at different loci were observed resulting in higher linkage disequilibrium. Our reference data of HLA profiles characterized at maximum resolution from many populations is useful for anthropological studies, unrelated donor searches, transplantation, and disease association studies.

HLA allele and haplotype frequencies in the Panamanian population

In this study, we report for the first time HLA allele and haplotype frequencies in the modern Panamanian population at a two-field (four digits) resolution level. Reported frequencies were calculated from genotype data for the HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 loci of 462 healthy unrelated Panamanian adults of Hispanic ethnicity. In addition to providing new insights on the allelic structure of the Panamanian population and its origin, these data are critical for better planning of healthcare strategies in the country and for future research exploring the association with certain chronic and infectious diseases.

HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 allele and haplotype frequencies defined by next generation sequencing in a population of East Croatia blood donors

Next-generation sequencing (NGS) is increasingly used in transplantation settings, but also as a method of choice for in-depth analysis of population-specific HLA genetic architecture and its linkage to various diseases. With respect to complex ethnic admixture characteristic for East Croatian population, we aimed to investigate class-I (HLA-A, -B, -C) and class-II (HLA-DRB1, -DQA1, -DQB1) HLA diversity at the highest, 4-field resolution level in 120 healthy, unrelated, blood donor volunteers. Genomic DNA was extracted and HLA genotypes of class I and DQA1 genes were defined in full-length, -DQB1 from intron 1 to 3′ UTR, and -DRB1 from intron 1 to intron 4 (Illumina MiSeq platform, Omixon Twin algorithms, IMGT/HLA release 3.30.0_5). Linkage disequilibrium statistics, Hardy-Weinberg departures, and haplotype frequencies were inferred by exact tests and iterative Expectation-Maximization algorithm using PyPop 0.7.0 and Arlequin v3.5.2.2 software. Our data provide first description of 4-field allele and haplotype frequencies in Croatian population, revealing 192 class-I and class-II alleles and extended haplotypic combinations not apparent from the existing 2-field HLA reports from Croatia. This established reference database complements current knowledge of HLA diversity and should prove useful in future population studies, transplantation settings, and disease-associated HLA screening.

Disaster victim identification by kinship analysis: the Lampedusa October 3rd, 2013 shipwreck

On October 3rd, 2013 a boat carrying more than 500 migrants coming mostly from the Horn of Africa (Eritrea, Somalia, Ethiopia) sank near Lampedusa, a small Italian Island in the middle of the Mediterranean Sea. The recovered bodies were examined by a forensic team, and post mortem data (anthropological and odontological records, and DNA) were collected for identification. Genetic profiles based on 16 autosomal STRs were acquired from both victims and putative relatives recruited following an international call. The final genetic database included 363 victims and 43 reference persons from 36 independent families recruited until mid-2017, who were missing 35 first-degree and 6 second-degree relatives. A pairwise blind search approach was used to identify familial relationships within the victims and between victims and putative relatives. Two statistics were calculated, the Identity by State (IBS) and the Identity by Descent (IBD), the latter by using the DVI module of the FAMILIAS3 software to compute LRs and posterior probabilities. The putative identifications were confirmed in pedigree analysis using the information provided by the relatives. In selected cases, additional autosomal and lineage (Y-chromosome and mtDNA) markers were typed. Some critical points were highlighted: the lack for accurate allele and haplotype frequencies in African populations, especially for the lineage markers, and the need for a shared approach to the biostatistical interpretation of the results in DVI. In the end, 29 first-degree (parent-child and full sibs) out of 35 missing (83%), and 3 out of 6 of second-degree relatives (50%) showed a high statistical confidence for a positive identification. This study represents the first attempt to systematically deal with the genetic identification of African migrants who died in the Mediterranean Sea. The methodological and statistical approach used in this study was proved to be reliable and appropriate for future genetic identifications in other similar mass disasters.

4-Locus high-resolution HLA allele and haplotype frequencies in admixed population from Nicaragua

A total of 155 Nicaraguan Mestizos from across the country were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, and -DRB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype identified was A*24:02:01-B*40:02:01-C*03:05-DRB1*04:07:01G, with an estimated frequency of 2.26%. No deviation from Hardy-Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database under the population name “Nicaragua Mestizo” and the identifier AFN3610.

Availability of HLA-allele-matched unrelated donors: estimation from haplotype frequency in the Japanese population.

A human leukocyte antigen (HLA)-matched unrelated donor is the primary alternative donor for allogeneic hematopoietic cell transplantation in Japan. In considering an optimal donor registry size, the availability of HLA-matched donors is important. In this study, the probability of finding an HLA-A, -B, -C, and -DRB1 allele-matched donor was estimated using two different methods based on the haplotype frequencies in the Japanese population: an actual measurement method (AMM) and a formula method (FM). According to AMM, the probabilities of finding an HLA-matched donor were 40.5% in 100,000 donors, 54.4% in 300,000, 60.0% in 500,000, and 63.4% in 700,000. On the other hand, according to FM, the probabilities were 47.8% in 100,000 donors, 59.9% in 300,000, 65.3% in 500,000, and 68.8% in 700,000. The probabilities increased by 8.6 or 7.7%, 3.2 or 3.1%, 2.1 or 1.9%, and 1.6 or 1.3% in AMM or FM, respectively, as the registry size increased by 100,000. The rate of increase in the probability of finding an HLA-matched donor will become smaller as the registry size increases due to the diversity of haplotypes. Therefore, it is important to set a target donor registry size for efficient donor recruitment by considering the haplotype frequencies in the population.

High-resolution HLA allele and haplotype frequencies in majority and minority populations of Costa Rica and Nicaragua: Differential admixture proportions in neighboring countries.

The HLA system shows the most extensive polymorphism in the human genome. Allelic and haplotypic frequencies of HLA genes vary dramatically across human populations. Due to a complex history of migration, populations in Latin America show a broad variety of admixture proportions, usually varying not only between countries, but also within countries. Knowledge of HLA allele and haplotype frequencies is essential for medical fields such as transplantation, but also serves as a means to assess genetic diversity and ancestry in human populations. Here, we have determined high-resolution HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies in a sample of 713 healthy subjects from three Mestizo populations, one population of African descent, and Amerindians of five different groups from Costa Rica and Nicaragua and compared their profiles to a large set of indigenous populations from Iberia, Sub-Saharan Africa, and the Americas. Our results show a great degree of allelic and haplotypic diversity within and across these populations, with most extended haplotypes being private. Mestizo populations show alleles and haplotypes of putative European, Amerindian, and Sub-Saharan African origin, albeit with differential proportions. Despite some degree of gene flow, Amerindians and Afro-descendants show great similarity to other Amerindian and West African populations, respectively. This is the first comprehensive study reporting high-resolution HLA diversity in Central America, and its results will shed light into the genetic history of this region while also supporting the development of medical programs for organ and stem cell transplantation.

Parasite infection of specific host genotypes relates to changes in prevalence in two natural populations of bumblebees

The antagonistic relationship between parasites and their hosts is strongly influenced by genotype-by-genotype interactions. Defense against parasitism is commonly studied in the context of immune system-based mechanisms and, thus, the focus in the search for candidate genes in host-parasite interactions is often on immune genes. In this study, we investigated the association between prevalence of parasite infection and host mitochondrial DNA (mtDNA) haplotypes in two natural populations of bumblebees (Bombus terrestris). The two most common haplotypes of the host populations, termed A and B, differ by a single nonsynonymous nucleotide substitution within the coding region of cytochrome oxidase I, an important player in metabolic pathways. We screened infection by Nosema bombi, a common endoparasite of bumblebees, and the corresponding host mtDNA-haplotype frequencies in over 1400 bumblebees between 2000 and 2010. The island population of Gotland showed lower mtDNA diversity compared to the mainland population in Switzerland. Over time, we observed large fluctuations in infection prevalence, as well as variation in host haplotype frequencies in both populations. Our long-term observation revealed that N. bombi infection of specific host genotypes is transient: We found that with increasing infection prevalence, proportionally more individuals with haplotype B, but fewer individuals with haplotype A were infected. This suggests that the presence of N. bombi in specific host genotypes relates to infection prevalence. This may be a result of parasite competition, or differential resilience of host types to ward off infections. The findings highlight the important role of host mtDNA haplotypes in the interaction with parasites.

P227 Determination of HLA -A, -B and - DRB1 alleles and HLA-A -B haplotype frequencies in Egyptians based on family study

Knowledge of allele and haplotype frequencies in human populations guides the search for an HLA- matched unrelated hematopoietic stem cell donor. A new algorithm developed by the National Marrow Donor program uses this information to predict the likelihood that a volunteer of a particular ethnicity will carry specific HLA alleles when typed at high resolution. In the present study, we determined the HLA-A,-B and -DRB1 alleles and HLA-A-B haplotype frequencies in Egyptians and compared them to various populations. Specificities of HLA-A, -B and -DRB1 loci were determined in 286 matched related donors of allogeneic hematopoeitic stem cell transplantation (AHSCT). Typing was performed using serologic and low resolution PCR- reverse sequence-specific oligonucleotide (rSSO) techniques. HLA-A-B haplotypes were defined by segregation analysis. The most frequent alleles for HLA class I HLA-A were: HLA-A2 (19.2%), A1 (15.8%), A30 (9.2%) and A24 (8.8%), for HLA-B, B41 (10.9%), B35 (10.2%), B44 (6%) and B50 (5.4%) and for DRB1∗13 (18.7%), ∗04 (15%) ,∗11(14.7%) and ∗03 (13.2%). The most frequent HLA-A-B haplotypes were: A24-B35 (3.8%), A2-B41 (3.4%), A1- B35 (3.4%) and A33-B14 (3.4%). This study report HLA allele and HLA-A-B haplotype patterns in Egyptians. These patterns were close to Jordanians and Lebanese and different from Saudi Arabians, Europeans, Americans and Asians. These data explain the difficulty of finding donors in world registries for Egyptian patients in need of a stem-cell transplant and highlight the need to for planning an Egyptian national unrelated donor registry to meet the demands of these patients.

Double origin of the racer goby (Babka gymnotrachelus) in Poland revealed with mitochondrial marker. Possible implications for the species alien/native status

&lt;p&gt;In mid-1990s racer goby, &lt;em&gt;Babka gymnotrachelus&lt;/em&gt;, penetrated to the Vistula and Western Bug rivers in Poland through the canal connecting the Baltic and the Black Sea basins, namely the Vistula and Dnieper drainages. In early 2000s, the species was reported from Polish section of the Strwiąż River that is an affluent of the Dniester River that drains to the Black Sea basin. According to the Polish legislation, the racer goby has been enlisted in as an alien invasive species that may pose threat to local biota. Our analysis of the mtDNA cytochrome b diversity revealed that the Vistula/Western Bug and Strwiąż populations are different genetic units. First one originated from the Dnieper River, while the second derives from the Dniester River. According to the results of mismatch analysis, both are in the stage of demographic and spatial expansion. The haplotype frequencies in population from the Vistula/Western Bug differ significantly from those in the source population in Dnieper, suggesting founder effect, possibly due to human-mediated introduction of low number of individuals. On the other side, the population in Strwiąż does not differ in structure from the one in Dniester, providing a hint towards spontaneous range expansion. Interpretation of our results in light of historical data lead to the conclusion that presence of racer goby in Strwiąż was probably overlooked in previous, spatially limited, studies. Thus, in Strwiąż the species should not be treated as alien, contrary to its status in the Vistula drainage. This double origin of racer goby populations in Poland creates a peculiar situation for national legislation procedures as one population is alien and invasive, while the other one is not. In light of our findings, the population from Strwiąż should be recognised as a special case. Steps should be undertaken to raise public awareness to prevent translocation of the gobies between the rivers to prevent deterioration of the evolutionarily isolated genetic pools of the Dnieper and of the Dniester basins. Our results illustrate the need for case studies upon genetic population structure, following appearance of new species in previously unoccupied water bodies, even on local scale. &lt;/p&gt;

Error catastrophe in populations under similarity-essential recombination.

Organisms are often more likely to exchange genetic information with others that are similar to themselves. One of the most widely accepted mechanisms of RNA virus recombination requires substantial sequence similarity between the parental RNAs and is termed similarity-essential recombination. This mechanism may be considered analogous to assortative mating, an important form of non-random mating that can be found in animals and plants. Here we study the dynamics of haplotype frequencies in populations evolving under similarity-essential recombination. Haplotypes are represented by a genome of B biallelic loci and the Hamming distance between individuals is used as a criterion for recombination. We derive the evolution equations for the haplotype frequencies assuming that recombination does not occur if the genetic distance is larger than a critical value G and that mutation occurs at a rate μ per locus. Additionally, uniform crossover is considered. Although no fitness is directly associated to the haplotypes, we show that frequency-dependent selection emerges dynamically and governs the haplotype distribution. A critical mutation rate μc can be identified as the error threshold transition, beyond which this selective information cannot be stored. For μ<μc the distribution consists of a dominant sequence surrounded by a cloud of closely related sequences, characterizing a quasispecies. For μ>μc the distribution becomes uniform, with all haplotypes having the same frequency. In the case of extreme assortativeness, where individuals only recombine with others identical to themselves (G=0), the error threshold results μc=1/4, independently of the genome size. For weak assortativity (G=B-1)μc=2(-(B+1)) and for the case of no assortativity (G=B) μc=0. We compute the mutation threshold for 0<G<B and show that, for large B, it depends only on the ratio G/B. We discuss the consequences of these results for recombination in viruses and for speciation.

LBP26: THE NIMA EFFECT IN CORD BLOOD TRANSPLANT (CBT): REAL OR A CONSEQUENCE OF BETTER HIGH RESOLUTION (HR) MATCHING IN THE NIMA MATCHED (NIMA+) GROUP?

Aim Studies have indicated improved clinical outcomes for CBT recipients with NIMA+ at HLA-A, B antigens, or -DRB1 alleles (standard matching for CBT). The frequencies of the HLA types for NIMA+ are associated with more common HLA and haplotypes. Therefore, NIMA+ may lead to better HR matching at HLA-A, B, and C. We have previously shown that HR matching at HLA- A, B, C, and DRB1 (X/8) decreased TRM in single CBT for acute leukemia. We evaluated CBT HR match association with NIMA +/- cases. Methods The cohort consisted of 705 CBTs from NMDP or Eurocord performed between 2000 and 2010. HR was available or imputed retrospectively using the NMDP’s HLA imputation algorithm, based on population haplotype frequencies, to infer the most likely phased genotype. 70% of recipients (HLA- A, B, C, DRB1 imputed alleles: N = 1052, 1024, 1170, 34, respectively) and 95% of CB units (HLA- A, B, C, DRB1 imputed alleles: N = 921, 908, 925, 20, respectively) had at least one allele imputed. HR match grades were determined at X/8. The distribution of NIMA+/- and HR match grades were then evaluated in the following groups based on the probability of TRM observed previously at 6-7/8, 4-5/8, and ⩽ 3/8. Results In the 5/6 cohort (N = 344) there were 17 NIMA+ (5%) and 327 NIMA- (95%). In the 4/6 (N = 361) cohort there were 39 NIMA + (11%) and 322 NIMA- (89%). The overall HR match counts were as follows: 322, 359, and 24 for 6-7/8, 4-5/8, and ⩽ 3/8, respectively. The table below shows the X/8 HR match grades stratified by NIMA+/-. The overall frequency of the 5/6 and 4/6 CBT cases having better HR match grades with NIMA+ vs. NIMA- was 100% vs. 79% (p = 0.04) and 10% vs. 13% (p = 0.86), respectively. Conclusion There was significant skewing in the 5/6 NIMA+ group to better HR matching. There was no significant difference in the 4/6 subset between the NIMA+/- groups. In this small population NIMA+ 5/6 had a better HR level matching. It remains to be seen whether the skewed HR matching is a driver of the previously observed NIMA effect.

Beta-globin gene haplotypes among cameroonians and review of the global distribution: is there a case for a single sickle mutation origin in Africa?

Studies of hemoglobin S haplotypes in African subpopulations have potential implications for patient care and our understanding of genetic factors that have shaped the prevalence of sickle cell disease (SCD). We evaluated HBB gene cluster haplotypes in SCD patients from Cameroon, and reviewed the literature for a global distribution. We reviewed medical records to obtain pertinent socio-demographic and clinical features for 610 Cameroonian SCD patients, including hemoglobin electrophoresis and full blood counts. RFLP-PCR was used to determine the HBB gene haplotype on 1082 chromosomes. A systematic review of the current literature was undertaken to catalogue HBB haplotype frequencies in SCD populations around the world. Benin (74%; n = 799) and Cameroon (19%; n = 207) were the most prevalent haplotypes observed among Cameroonian patients. There was no significant association between HBB haplotypes and clinical life events, anthropometric measures, hematological parameters, or fetal hemoglobin (HbF) levels. The literature review of the global haplotype distributions was consistent with known historical migrations of the people of Africa. Previously reported data from Sudan showed a distinctly unusual pattern; all four classical haplotypes were reported, with an exceptionally high proportion of the Senegal, Cameroon, and atypical haplotypes. We did not observe any significant associations between HBB haplotype and SCD disease course in this cohort. Taken together, the data from Cameroon and from the wider literature suggest that a careful reassessment of African HBB haplotypes may shed further light on the evolutionary dynamics of the sickle allele, which could suggest a single origin of the sickle mutation.

Determination of HLA-A, -C, -B, -DRB1 allele and haplotype frequency in Japanese population based on family study.

The present study investigates the human leucocyte antigen (HLA) allele and haplotype frequencies in Japanese population. We carried out the frequency analysis in 5824 families living across Japanese archipelago. The studied population has mainly been typed for the purpose of transplant, especially the hematopoietic stem cell transplantation (HSCT). We determined HLA class I (A, B, and C) and HLA class II (DRB1) using Luminex technology. The haplotypes were directly counted by segregation. A total of 44 HLA‐A, 29 HLA‐C, 75 HLA‐B, and 42 HLA‐DRB1 alleles were identified. In the HLA haplotypes of A‐C‐B‐DRB1 and C‐B, the pattern of linkage disequilibrium peculiar to Japanese population has been confirmed. Moreover, the haplotype frequencies based on family study was compared with the frequencies estimated by maximum likelihood estimation (MLE), and the equivalent results were obtained. The allele and haplotype frequencies obtained in this study could be useful for anthropology, transplantation therapy, and disease association studies.