Influence of Hemoglobin S Haplotypes on the Responses to Hydroxyurea Treatment in Children with Sickle Cell Disease in Abidjan, Côte d’Ivoire

Background: In Côte d’Ivoire so far, the circulating haplotypes have been inferred on the phenotypic profiling of SCD patients. The impact of the circulating haplotypes on the use of Hydroxyurea has not been assessed yet. Therefore the objective of this study is to identify in Abidjan the HbS haplotypes that modulate HU treatment responses. Methods: In a cross-sectional descriptive and analytical study, children aged 5 to 15 years with SCD, and carrying the hemoglobin phenotypes SSFA2 and SFA2, were recruited into a HU treatment cohort. Various parameters on the haplotypes and the outcomes of the treatment were analyzed. Results: Thirty nine children with SCD were included. The phenotypic profile of the cohort was 86.6% of SSFA2 and 15.4% of SFA2. Three haplotypes were found, the Benin haplotype, the Senegal haplotype, and an atypical one. The participants belonged to three genotypes, Benin/atypical (64.1%), Benin/Senegal (33.3%) and Senegal/Senegal (2.6%). Overall, HU treatment was successful in all haplotypes with 12 out of 39 patients failing treatment after 12 months in the Benin haplotype group. The association between HU treatment success and the Benin haplotype was found in terms of the decrease in the number of white blood cells and the students missing class. Conclusion: The study revealed that inferring haplotype based on the phenotypic profile could be inaccurate. The proportion of atypical haplotype that were not previously described in Côte d’Ivoire was high. All the haplotypes seemed to be associated with HU treatment success but some patients with Benin haplotype did not respond well.

Association of Haplotypes in Exon 4 of KLK2 Gene with Raised Serum Prostate-Specific Antigen

The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X2 = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.

Mitochondrial Haplotypes suggest Genetic Component for Habitat Preference in Blue Crabs

Atlantic blue crabs(Callinectes sapidus)are ecologically and commercially fundamental.Life stages are punctuated with migration.Adults and juveniles live in estuaries and sounds.Larval stages develop in the coastal ocean.Juvenile and adult crabs occupy habitats from high salinities to fresh water.We determined whether maturing juvenile and adult blue crab habitat use is reflected in mitochondrial cytochrome oxidase 1 haplotypes.High salinity crabs had lower haplotype diversity(0.7260±.03900)compared to spawning crabs(0.9841±.00021)and low salinity crabs(0.94154±.00118).Significant pairwise differences in haplotypes were found between high salinity and spawning crabs(Nm=0.26018,p<0.001),and between high salinity and low salinity crabs(Nm=0.19482,p<0.001)indicating a lack of gene flow.Crabs from high salinity had highly significant genetic differentiation compared to spawning crabs(Fst=0.11830,p<0.001)and low salinity crabs(Fst=0.09689,p<0.001).Results support the hypothesis that genetics influence habitat selection.Crab larvae mix in the coastal ocean but occupy specific habitats upon return to sounds and estuaries.These findings have implications for the management of fisheries.

Frequency of celiac disease and distribution of HLA-DQ2/DQ8 haplotypes among siblings of children with celiac disease

BACKGROUND Celiac disease(CD)is a multifactorial disease,but genetic factors play a major role in its etiology.It has been known that human leucocyte antigen(HLA)-DQ2/DQ8 haplotypes are one of the most important predisposing genetic factors.The risk of developing CD in first-degree relatives and especially siblings of celiac patients is quite high because of having the same HLA haplotypes.AIM To evaluate the frequency of CD and the distribution of the HLA-DQ2/DQ8 haplotypes in siblings of celiac patients.METHODS Patients with biopsy-proven CD and their siblings were included in the study;those who did not have HLA genotyping were excluded from the study.All siblings were on a gluten-containing diet.The HLA genotyping,tissue transglutaminase antibody IgA antibody test,and total IgA test were performed in all participants.RESULTS A total of 57 celiac patients and their 112 siblings were included in the study.The mean age of celiac patients and siblings were 10.30±3.87 years and 9.90±6.11 years,respectively.HLA-DQ2/DQ8 alleles were detected in 98.2%of patients with CD and 90.2%of siblings of celiac patients.HLA-DQ genotypes were present in all siblings diagnosed with CD.Tissue transglutaminase antibody IgA test was found to be positive in 16 siblings.CD was diagnosed in 12 siblings(10.7%)by intestinal biopsy.CONCLUSION The prevalence of CD was found to be 10.7%in siblings of celiac patients in our study.One-third of the siblings diagnosed with CD were asymptomatic.We detected HLA-DQ alleles in 98.2%of celiac patients and 100%in siblings diagnosed with CD.In addition,1 of the 2 siblings was diagnosed with CD 1 year later and the other 4 years later.Therefore,we suggest that siblings of celiac patients should be followed up with clinical findings as well as HLA analysis and serological examination.Since the risk of developing CD is much higher in asymptomatic siblings,we recommend that siblings should be screened for CD even if they are asymptomatic.

ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population

AIM:To evaluate the association between the geneticpolymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.METHODS:The study subjects were 477 age-and sex-matched case-control pairs.Genotyping was performed for 15 single nucleotide polymorphisms(SNPs)in ITGA1.The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models.Multiple testing corrections were carried out following methodology for controlling the false discovery rate.Gene-based association tests were performed using the versatile gene-based association study(VEGAS)method.RESULTS:In the codominant model,the ORs for SNPs rs2432143(1.517;95%CI:1.144-2.011)and rs2447867(1.258;95%CI:1.051-1.505)were statistically significant.In the dominant model,polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors,with ORs of 1.337(95%CI:1.029-1.737)and 1.412(95%CI:1.061-1.881),respectively.In the recessive model,only the rs2432143 polymorphism was significant(OR=1.559,95%CI:1.150-2.114).The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model(OR=0.602,95%CI:0.212-0.709,P=0.021)and the dominant model(OR=0.653,95%CI:0.483-0.884).The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test.In the dominant model,the A-T type of ITGA1 haplotype block 2 was a significant risk factor(OR=1.341,95%CI:1.034-1.741).SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and,thus,to the risk of developing gastric cancer.CONCLUSION:ITGA1 gene SNPs rs1862610,rs2432143,and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.

The distribution of HLA-A,-B,and-DRB1 alleles and haplotypes in inhabitants of Guizhou Province of China

The present study was aimed to analyze the frequencies of human leukocyte antigen （HLA）-A, -B, and -DRB1 alleles and A-B-DRBI, A-B, A-DRB1 and B-DRB1 haplotypes in inhabitants of Guizhou province, China. All samples were typed in the HLA-A,-B, and -DRB1 loci using the polymerase chain reaction-reverse sequence spe- cific oligonucleotide probe （PCR-rSSOP） method and HLA polymorphisms were analyzed. A total of 18 HLA-A, 31 HLA-B, and 13 HLA-DRB1 alleles were found in the Guizhou population. The first two frequent alleles in the HLA-A, -B, and -DRB1 loci were A＊1 1（30.72%） and A＊02（30.65%）, B＊40（16.27%） and B＊46（16.27%）, and DRBl＊09（15.91%） and DRBl＊15（13.51%）, respectively. The most common haplotype was A＊02-B＊46- DRBl＊09（5.59%） in A-B-DRB1, A＊02-B＊46（I 1.73%） in A-B, B＊46-DRBl＊09（7.49%） in B-DRB1, and A＊02- DRBl＊09（8.08%） in A-DRB1. Some baplotypes with strong linkage disequilibrium （LD） were found not only in the common haplotypes, such as A＊33-B＊58, B＊30-DRB1＊07, and B＊33-DRB1＊03, but also in the rare haplotypes, such as A＊01-B＊37, B＊37-DRB1＊10, and A＊01-DRB1＊10. Guizhou inhabitants shared some characteristics of the Southern Chinese population but also had their own unique features. Overall, HLA polymorphism in Guizhou population was more consistent with that of Chengdu population than that of other populations in China.

Haplotypes at the 5′-Flanking Region of Peroxisome Proliferator-Activated Receptor γ Gene and Their Association with the Growth and Body Composition Traits in Chickens

Peroxisome proliferator-activated receptor g（PPARg） is an important regulator of chicken preadipocyte proliferation and differentiation.In this study,polymorphisms were detected by DNA sequencing,PCR-RFLP and some other methods and three polymorphisms（g.-1784_-1768del17,c.-1241GA and c.-75GA） were found in the 5＇ flanking region of PPARg gene.Growth and body composition traits were measured in the 8th-10th generation populations of the Northeast Agricultural University broiler lines were divergently selected for abdominal fat content.Polymorphisms among individuals were screened in the above populations.The haplotype-based association analysis on growth and body composition traits was carried out.The association analysis showed that haplotypes based on three polymorphisms at 5＇ flanking region of PPARg gene were significantly associated with abdominal fat weight（AFW）,abdominal fat percentage（AFP,AFW/BW7）,liver weight（LW）,liver weight percentage（LFP,LW/BW7）,shank length（ShL）,femur weight（FeW）,keel length（KeL）,and metatarsus circle（MeC）（P0.05） and suggestive significantly associated with pectoralis major weight（PMaW）,pectoralis minor weight（PMiW）,pectoralis minor weight percentage（PMiWP,PMiW/BW7）,and metatarsus length（MeL）（P0.2）.The least square analysis showed that the birds with BGA haplotype had significantly higher AFW and AFP than the birds with other haplotypes（P0.05）.The birds with AAG haplotype had significantly higher LW and LW/BW than the birds with other haplotypes（P0.05）.The birds with AAG haplotype had significantly higher PMiW and PMiW/BW than the birds with other haplotypes（P0.05）.The birds with AAG haplotype had significantly higher ShL,FeW,MeL,MeC and KeL than the birds with AGG haplotypes（P0.05）.The results in this study revealed that QTL affecting fatness traits may exist in 5＇ flanking region of PPARg gene in chickens and PPARg gene might be one of the genes having important influences on the growth and bone traits in chickens.

Primary study on correlation betweenβ_2-adrenoceptor haplotypes and asthma in children of Han nationality in Chongqing

Objective:To investigatethecorrelationbetweenβ 2 -adrenergicreceptors(β 2 -AR)haplotypesandasthmaof Hannationalitychildrenin Chongqingregion.Methods:PCRandrestrictionfragmentanalysiswereusedto study16,27lociof theβ 2 -ARpolymorphismin76unrelatedasthmaticchildrenandin100healthychildrenandadultsof Hannationali-ty as control.A statisticalanalysisof thecorrelationbetweenglycine(Gly)16allele,Gly16/glutamine(Gln)27haplotype andasthmaticclinicalstatuswas carriedout.Results:Therewas no significantincreaseof thefrequencyof Gly16and Gln27alleleintheasthmaticgroupas comparedwiththecontrolgroup(P>0.05).Therewasa significantincreaseof the frequencyof Gly16alleleandGly16/Gln27haplotypein severeasthmaticcasesthanin themildandmoderateasthmatic ones(P<0.01,0.05).Conclusion:Itis consideredthatasthmais notcausedby GlyandGlnallelesofβ 2 -ARpolymor-phisms.Gly16alleleandGly16/Gln27haplotypearepossiblycorrelatedwiththeseverityof theclinicalmanifestationsin thechildrenof HannationalityinChongqing.

MDR1 Haplotypes and G2677T/A Polymorphism Predict Imatinib Response in Tunisian Patients with Chronic Myeloid Leukemia

Background: The role of human multidrug resistance gene (MDR1) SNPs in the interindividual variability of imatinib mesylate (IM) response has received considerable attention. We aimed to study the association between SNPs of the MDR1 gene (C1236T, G2677T/A, C3435T) and IM response in chronic myeloid leukemia (CML) patients. Method: A retrospective case-control study was conducted on 48 patients with CML undergoing IM therapy. All patients were genotyped using PCR-RFLP method. Results: The genotype and allele frequencies of C1236T and C3435T were not significantly different between CML patients responders and non-responders to IM (p > 0.05). The frequencies of 2677T allele and 2677TT genotype were significantly increased in CML patients IM responders which as compared with IM non-responders (50% vs 26.9%, p = 0.013 and 27.3% vs 3.8%, p = 0.029 respectively). Whereas the 2677AA genotype and CAC haplotype were found only in CML patients IM non-responders (15.4%). Conclusion: Pretreatment genotyping of G2677A/T appears to be useful for predicting IM resistance, which may allow the best choice of drug treatment for CML patients.

Variable <i>β</i>-globin haplotypes in Saudi <i>β</i>thalassemia population

Twenty two haplotypes were generated from a pool of 60 unrelated Saudi β thalassemia major patients using previously described restriction sites in the β globin gene. Linkage disequilibrium analysis of the polymorphic sites was also conducted, a few identified haplotypes were novel while the remainder was previously reported, haplotype1222212 was the most frequent haplotype in the study group and a strong linkage disequilibrium between two polymorphic restriction sites in these β thalassemia patients was uncovered.

Single Nucleotide Polymorphisms and Haplotypes in Vascular Endothelial Growth Factor Gene and Residual Ridge Resorption of Mandible in Korean Population

The tooth extraction is a routine surgical procedure in the dental treatment where the healing process results in a saddle-shaped residual ridge in the edentulous jaw. There are substantial differences among individuals in the end result. In some cases, there is excessive bone atrophy, which complicates the dental restorative treatment. The alveolar ridge receives the mechanical load continuously from the periodontal ligament connected to the teeth and it diminishes dramatically as a consequence of dental extraction;thus it is believed the continuing pattern of the alveolar bone resorption is related to this change. The reduced partial pressure of oxygen is the most prominent event from the reduced mechanical load. Vascular Endothelial Growth Factor (VEGF), regulated by HIF-1, reported close association with angiogenesis and bone turn over, where partial oxygen pressure has changed. Therefore the genetic association between Single Nucleotide Polymorphsim (SNP) of VEGF gene and RRR was investigated. 120 subjects (70.93 ± 9.28 years) which were treated at Dental clinic of Yonsei University with edentulous mandible were recruited. Mandibular bone height was measured following the protocol of the American College of Prosthodontists. Three variants, rs1570360, rs25648, and rs3025039 in VEGF from previous study, were used as tag-SNPs and genotyping for the study. Student’s t-test and ANOVA were used for statistical analysis. There was a notable association with rs1570360 (P = 0.051) in dominant group and haplotype A-C-C showed a statistically significant association with RRR in dominant group (P = 0.042). Results of this study may be useful in developing novel genetic diagnostic tests and identifying Koreans susceptible to developing severe RRR after dental extraction.

A Piece of a Puzzle of Haplotypes for the Indian Ocean Hawksbill Turtle

The Indian Ocean basin has much to reveal in what concerns marine turtles. Its regional management units (RMUs) are still lacking molecular data to define conservation strategies and priorities. Vamizi Island is one of the best known rookeries in the north of the Mozambique Channel. A mitochondrial DNA analysis revealed 14 haplotypes for the hawksbill turtle’s nesting and foraging in/near Vamizi, twelve of which were new in 2011. Though more studies inside the Channel are needed, Vamizi Island possibly contributes with hatchlings for other locations. More knowledge is important to define priorities for management units inside the Indian Ocean.

Seed Storability of CIMMYT Core Wheat Germplasm Panel and Their Haplotypes in <i>Lipoxygenase</i>Locus

Seed storability (SS), also called seed longevity, is a valuable trait for seed banks and providing reliable crop seeds to farmers, which is usually negatively correlated to lipoxygenase (LOX) activity. In this study, the seed storability of 60 accessions of CIMMYT core wheat germplasm panel (CIMCOG) was investigated through artificial aging (AA) test, including three parameters relative germination potential (RGP), relative germination rate (RGR) and relative seedling vigor index (RVI). Significant positive relationships were observed among RGP, RGR and RVI. And the genotypes at three LOX activity related QTLs/genes QLpx.caas-4B, QLpx.caas-1AL and TaLOX-B1 were also identified with published trait-associated molecular markers. For QLpx.caas-4B, a total of five alleles were detected at the locus of Xgwm251, and one marker-trait association was identified for RVI. Four and two alleles were detected at the loci of QLpx.caas-1AL and TaLoxB1 that were significantly associated with RGP, RGR and RVI, respectively. A total of 9 haplotypes were detected at three lipoxygenase activity related gene loci, and the haplotype of three lipoxygenase loci showed a significant association with RGP, RGR and RVI. The haplotype of Xgwm251-125bp + Xwmc312-247bp + TaLox-B1b produced seeds with the best storability in the CIMCOG, which could benefit the breeding for wheat with good seed storability.

Peroxisome Proliferator-activated Receptor-γ2 Pro12Ala and C-689T Polymorphisms and Haplotypes Affect the Profiles of Coronary Heart Disease in Diabetic Chinese People

Objectives Peroxisome proliferator-activated receptor-γ2（PPARγ2） variant Pro12Ala was demonstrated with risk of coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Another variant C-689T in the promoter was reported with lower receptor activity but lack of reports on association between C-689T and CHD or T2DM. Methods A total of 351 subjects without CHD and T2DM （controls） and 125 patients with CHD and T2DM （cases） were enrolled in our case-control study. Polymerase chain reaction-restricted fragments length polymorphism （PCR-RFLP） was used to detect Pro12Ala and C-689T polymorphisms. And effects on CHD merged with T2DM of the two polymorphisms were analyzed in individual and haplotype analyses. Results In the study, Pro12Pro, Pro12Ala and Ala12Ala genotype frequencies were 92.9%, 6.8% and 0.3% in controls; 92.8%, 7.2% and 0.0% in cases respectively whilst CC, CT and TT genotype frequencies were 93.4%, 6.3% and 0.3% in controls; 92.8%, 7.2% and 0.0% in cases respectively. Pro12Ala and C-689T polymorphisms were in strong linkage disequilibrium （D＇=0.81, P=0.000） and the observed haplotype frequency of Pro-C, Pro-T, Ala-C and Ala-T was 0.957, 0.006, 0.008 and 0.028 respectively. No significant associations were detected between the two polymorphisms and CHD merged with T2DM in either individual or haplotype analyses. In subjects with obesity [body mass index （BMI）≥25 kg/m^2], we found that both Pro12Ala and C-689T polymorphisms were associated with BMI. In haplotype analyses, we found that Pro12Ala and C-689T haplotypes had associations with systolic blood pressure in total population, with BMI, waist circle and total cholesterol（TC） in obesity subgroup and with fasting blood glucose and TC in males. Conclusions PPARγ2 Pro12Ala and C-689T polymorphisms and haplotypes affect the profiles of CHD merged with T2DM in Chinese Han people.

Genome resources for the elite bread wheat cultivar Aikang 58 and mining of elite homeologous haplotypes for accelerating wheat improvement

Despite recent progress in crop genomics studies,the genomic changes brought about by modern breeding selection are still poorly understood,thus hampering genomics-assisted breeding,especially in polyploid crops with compound genomes such as common wheat(Triticum aestivum).In this work,we constructed genome resources for the modern elite common wheat variety Aikang 58(AK58).Comparative genomics between AK58 and the landrace cultivar Chinese Spring(CS)shed light on genomic changes that occurred through recent varietal improvement.We also explored subgenome diploidization and divergence in common wheat and developed a homoeologous locus-based genome-wide association study(HGWAS)approach,which was more effective than single homoeolog-based GWAS in unraveling agronomic trait-associated loci.A total of 123 major HGWAs loci were detected using a genetic population derived from AK58 and cs.Elite homoeologous haplotypes(HHs),formed by combinations of subgenomic homoeologs of the associated loci,were found in both parents and progeny,and many could substantially improve wheat yield and related traits.We built a website where users can download genome assembly sequence and annotation data for AK58,perform blast analysis,and run JBrowse.Our work enriches genome resources for wheat,provides new insights into genomic changes during modern wheat improve-.ment,and suggests that efficientmining of elite HHs can make a substantial contribuutionto genomics-assisted breeding in common wheat and other polyploid crops.

Interleukin 6 and interferon gamma haplotypes are related to cytokine serum levels in dogs in an endemic Leishmania infantum region

Background The Ibizan Hound is a canine breed native to the Mediterranean region,where leishmaniasis is an endemic zoonosis.Several studies indicate a low prevalence of this disease in Ibizan Hound dogs,whereas other canine breeds present a high prevalence.However,the underlying molecular mechanisms still remain unknown.The aim of this work is to analyse the relationship between serum levels of cytokines and the genomic profiles in two canine breeds,Ibizan Hound(resistant canine breed model)and Boxer(susceptible canine breed model).Methods In this study,we analyse the haplotypes of genes encoding cytokines related to immune response of Leishmania infantum infection in twenty-four Boxers and twenty-eight Ibizan Hounds apparently healthy using CanineHD DNA Analysis BeadChip including 165,480 mapped positions.The haplo.glm extension of haplo.score was used to perform a General Linear Model(GLM)regression to estimate the magnitude of individual haplotype effects within each cytokine.Results Mean levels of interferon gamma(IFN-γ),interleukin 2(IL-2)and IL-18 in Boxer dogs were 0.19±0.05 ng/ml,46.70±4.54 ng/ml,and 36.37±30.59 pg/ml,whereas Ibizan Hound dogs present 0.49±0.05 ng/ml,64.55±4.54 ng/ml,and 492.10±31.18 pg/ml,respectively.The GLM regression shows fifteen haplotypes with statistically significant effect on the cytokine serum levels(P<0.05).The more relevant are IL6-CGAAG and IFNG-GCA haplotypes,which increase and decrease the IL-2,IL-8 and IFN-γserum levels,respectively.Conclusions Haplotypes in the IFNG and IL6 genes have been correlated to serum levels of IFN-γ,IL-2 and IL-18,and a moderate effect has been found on IL8 haplotype correlated to IL-8 and IL-18 serum levels.The results indicate that the resistance to L.infantum infection could be a consequence of certain haplotypes with a high frequency in the Ibizan Hound dog breed,while susceptibility to the disease would be related to other specific haplotypes,with high frequency in Boxer.Future studies are needed to elucidate whether these differences and haplotypes are related to different phenotypes in immune response and expression gene regulation to L.infantum infections in dogs and their possible application in new treatments and vaccines.

Convergence of Y Chromosome STR Haplotypes from Different SNP Haplogroups Compromises Accuracy of Haplogroup Prediction

The paternally inherited Y chromosome has been widely used in forensics for personal identification, in anthropology and population genetics to understand origin and migration of human populations, and also in medical and clinical studies （Wang and Li, 2013; Wang et al., 2014）. There are two kinds of extremely useful markers in Y chromosome, single nucle- otide polymorphism （SNP） and short tandem repeats （STRs）. With a very low mutation rate on the order of 3.0 x 10-8 mutations/nucleotide/generation （Xue et al., 2009）, SNP markers have been used in constructing a robust phylogeny tree linking all the Y chromosome lineages from world pop- ulations （Karafet et al., 2008）. Those lineages determined by the pattern of SNPs are called haplogroups. That is to say, we have to genotype an appropriate number of SNPs in order to assign a given Y chromosome to a haplogroup. Compared with SNPs, the mutation rates of STR markers are about four to five orders of magnitude higher （Gusmgo et al., 2005; Ballantyne et al., 2010）. Typing STR has advantages of saving time and cost compared with typing SNPs in phylogenetic assignment of a Y chromosome （Wang et al., 2010）. A set of STR values for an individual is called a haplotype. Because of the disparity in mutation rates between SNP and STR, one SNP haplogroup could actually comprise many STR haplotypes （Wang et al., 2010）. It is most interesting that STR variability is clustered more by haplogroups than by populations （Bosch et al., 1999; Behar et al., 2004）, which indicates that STR haplotypes could be used to infer the haplogroup information of a given Y chromosome. There has been increasing interest in this cost- effective strategy for predicting the haplogroup from a given STR haplotype when SNP data are unavailable. For instance, Vadim Urasin＇s YPredictor （http：//predictor.ydna.ru/）, Whit Atheys＇ haplogroup predictor （http：//www.hprg.com/hapest5/） （Athey, 2005, 2006）, and haplogroup classifier of Arizona University （Schlecht et al., 2008） have been widely employed in previous studies for haplogroup prediction （Larmuseau et al., 2010; Bembea et al., 2011; Larmuseau et al., 2012; Tarlykov et al., 2013）.

Impact of Human Leukocyte Antigen Loci and Haplotypes on Intestinal Acute Graft-versus-host Disease after Human Leukocyte Antigen-matched Sibling Peripheral Blood Stem Cell Transplantation

Background： Acute graft-versus-host disease （aGVHD） is a common and severe complication of allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Some studies have found that the presence of certain specific human leukocyte antigen （HLA） loci could affect the occurrence of aGVHD. Meanwhile, the impact of HLA haplotypes on aGVHD has been rarely studied. This study aimed to investigate the effects of HLA loci and haplotypes on intestinal aGVHD. Methods： Totally, 345 consecutive patients undergoing first HLA-matched sibling peripheral blood stem cell transplantation （PBSCT） from February 2004 to June 2013 at Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were enrolled in this study. HLA loci and haplotypes of recipients with frequency over 5% were searched and their effects on intestinal aGVHD were investigated. Other important factors including donor age, recipient age, donor-recipient sex combinations, and conditioning regimens were also evaluated using logistic regression. Pure upper gastrointestinal tract aGVHD without diarrhea was excluded because the histological proof was unavailable. The follow-up end-point was 6 months after HSCT. Results： The cumulative incidence of intestinal aGVH D was 19.4%, with 18.0% of the patients classified as classic aGVH D and 1.4% as persistent, recurrent, or late aGVH D. Multivariate analysis showed that HLA-A31 locus （odds ratio [OR] 2.893, 95% confidence interval [CI] [1.054, 7.935], P = 0.039）, H LA B40-DR 15 （OR 3.133, 95% CI [1.250, 7.857], P = 0.015）, and HLA B46-DR9 haplotypes （OR 2,580, 95% CI l1.070, 6.220], P- 0.035）, fizmale donor for male recipient （OR 2.434, 95% （27 [1.319, 4.493], P = 0.004） were risk factors tbr intestinal aGVHD. Conclusion： The presence of certain HLA loci and haplotypes may influence the occurrence of intestinal aGVHD in PBSCT with HLA-identical sibling donors.

Genome-wide association study of grain micronutrient concentrations in bread wheat

Bread wheat(Triticum aestivum)is a staple food crop worldwide.The genetic dissection of important nutrient traits is essential for the biofortification of wheat to meet the nutritional needs of the world's growing population.Here,45,298 single-nucleotide polymorphisms(SNPs)from 55K chip arrays were used to genotype a panel of 768 wheat cultivars,and a total of 154 quantitative trait loci(QTLs)were detected for eight traits under three environments by genome-wide association study(GWAS).Three QTLs(qMn-3B.1,qFe-3B.4,and qSe-3B.1/qFe-3B.6)detected repeatedly under different environments or traits were subjected to subsequent analyses based on linkage disequilibrium decay and the P-values of significant SNPs.Significant SNPs in the three QTL regions formed six haplotypes for qMn-3B.1,three haplotypes for qFe-3B.4,and three haplotypes for qSe-3B.1/qFe-3B.6.Phenotypic analysis revealed significant differences among haplotypes.These results indicated that the concentrations of several nutrient elements have been modified during the domestication of landraces to modern wheat.Based on the QTL regions,we identified 15 high-confidence genes,eight of which were stably expressed in different tissues and/or developmental stages.TraesCS3B02G046100 in qMn-3B.1 and TraesCS3B02G199500 in qSe-3B.1/qFe-3B.6 were both inferred to interact with metal ions according to the Gene Ontology(GO)analysis.TraesCS3B02G199000,which belongs to qSe-3B.1/qFe-3B.6,was determined to be a member of the WRKY gene family.Overall,this study provides several reliable QTLs that may significantly affect the concentrations of nutrient elements in wheat grain,and this information will facilitate the breeding of wheat cultivars with improved grain properties.

Insights into genetic diversity and phenotypic variations in domestic geese through comprehensive population and pan-genome analysis

Background Domestic goose breeds are descended from either the Swan goose(Anser cygnoides)or the Greylag goose(Anser anser),exhibiting variations in body size,reproductive performance,egg production,feather color,and other phenotypic traits.Constructing a pan-genome facilitates a thorough identification of genetic variations,thereby deepening our comprehension of the molecular mechanisms underlying genetic diversity and phenotypic variability.Results To comprehensively facilitate population genomic and pan-genomic analyses in geese,we embarked on the task of 659 geese whole genome resequencing data and compiling a database of 155 RNA-seq samples.By constructing the pan-genome for geese,we generated non-reference contigs totaling 612 Mb,unveiling a collection of 2,813 novel genes and pinpointing 15,567 core genes,1,324 softcore genes,2,734 shell genes,and 878 cloud genes in goose genomes.Furthermore,we detected an 81.97 Mb genomic region showing signs of genome selection,encompassing the TGFBR2 gene correlated with variations in body weight among geese.Genome-wide association studies utilizing single nucleotide polymorphisms(SNPs)and presence-absence variation revealed significant genomic associations with various goose meat quality,reproductive,and body composition traits.For instance,a gene encoding the SVEP1 protein was linked to carcass oblique length,and a distinct gene-CDS haplotype of the SVEP1 gene exhibited an association with carcass oblique length.Notably,the pan-genome analysis revealed enrichment of variable genes in the“hair follicle maturation”Gene Ontology term,potentially linked to the selection of feather-related traits in geese.A gene presence-absence variation analysis suggested a reduced frequency of genes associated with“regulation of heart contraction”in domesticated geese compared to their wild counterparts.Our study provided novel insights into gene expression features and functions by integrating gene expression patterns across multiple organs and tissues in geese and analyzing population variation.Conclusion This accomplishment originates from the discernment of a multitude of selection signals and candidate genes associated with a wide array of traits,thereby markedly enhancing our understanding of the processes underlying domestication and breeding in geese.Moreover,assembling the pan-genome for geese has yielded a comprehensive apprehension of the goose genome,establishing it as an indispensable asset poised to offer innovative viewpoints and make substantial contributions to future geese breeding initiatives.