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2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Dai Peng ◽  
Zhao Ganye ◽  
Sun Gege ◽  
Xia Yanjie ◽  
Liu Ning ◽  
...  

Abstract Background Phenylketonuria (PKU) is a metabolic disease that can cause severe and irreversible brain damage without treatment. Methods Here we developed a non-invasive prenatal diagnosis (NIPD) technique based on haplotypes via paired-end molecular tags and weighting algorithm and applied it to the NIPD of PKU to evaluate its accuracy and feasibility in the early pregnancy. A custom-designed hybridization probes containing regions in phenylalanine hydroxylase (PAH) gene and its 1 Mb flanking region were used for target sequencing on genomic and maternal plasma DNA (7–13 weeks of gestation) to construct the parental haplotypes and the proband’s haplotype. Fetal haplotype was then inferred combined with the parental haplotypes and the proband’s haplotype. The presence of haplotypes linked to both the maternal and paternal mutant alleles indicated affected fetuses. The fetal genotypes were further validated by invasive prenatal diagnosis in a blinded fashion. Results This technique has been successfully applied in twenty-one cases. Six fetuses were diagnosed as patients carrying both of the mutated haplotypes inherited from their parents. Eleven fetuses were carriers of one heterozygous PAH variants, six of which were paternal and five of which were maternal. Four fetuses were absence of pathogenic alleles. All results were consistent with the prenatal diagnosis through amniotic fluid. Conclusions The results showed that our new technique applied to the genotyping of fetuses with high risk for PKU achieves an accurate detection at an early stage of pregnancy with low fetal fraction in cell free DNA.


2021 ◽  
Vol 55 (6) ◽  
pp. 863-869
Author(s):  
C. Zhang ◽  
H. J. Zhao ◽  
J. Wang ◽  
W. Y. Zhou ◽  
T. J. Zhang ◽  
...  

Author(s):  
Ravinder Singh ◽  
Ankita Gurao ◽  
S.K. Mishra ◽  
S.K. Niranjan ◽  
Vikas Vohra ◽  
...  

Background: HSP70 (Heat Shock Protein 70), plays a crucial role in nascent protein folding; the added challenges due to physiological factors demand stringent role-playing of such chaperones for tropical livestock such as water buffalo (Bubalus bubalis). Therefore to evaluate the variations at nucleotide level in HSP70 that could potentially unravel the molecular basis of thermal adaptation in the riverine buffalo breeds of India, the current study was targeted to sequence the CDS (Coding Sequence) and UTR (Untranslated Region) of the gene in a panel of 16 Indian riverine buffalo breeds. Methods: Blood samples were collected and genomic DNA was isolated followed by PCR standardized for the amplification of different fragments of the HSP70 gene using different sets of primer pairs covering the entire coding region and 5’UTR. Multiple amplicons generated to cover the entire gene were sequenced. Sequences were further analyzed manually for the identification of heterozygous animals to detect the polymorphic nucleotide sites and variation between breeds documented. Result: The HSP70 results suggest, the highly conserved nature of gene in buffalo. The only non-synonymous polymorphic site was found in the Toda buffalo breed (g.SNPC greater than T at position 14), resulting in amino acid change 5M greater than T. A total of 7 polymorphic sites were found in the 5’UTR flanking region. Additionally, two insertion/deletions (INDEL) of 30 and 1 nucleotide length were found in the 5’UTR.


Author(s):  
Azhaguraja Manoharan ◽  
S. Sankaralingam ◽  
P. Anitha ◽  
Binoj Chacko ◽  
T.V. Aravindakshan

Background: The avian prolactin gene is highly conserved, located on chromosome number 2 and most sequence polymorphisms occurs in the 5’ flanking region, 3’ flanking region, and the coding region of signal peptide. The present study was aimed at the identification of SNP C-2402T of prolactin gene and its association with production traits in White Leghorn chicken. Methods: A total of 200 birds of White Leghorn were selected from All India Co-ordinated Research Project on Poultry improvement (AICRP) farm, Mannuthy. Genomic DNA was isolated from venous blood. Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis was done to identify the SNP C-2402T of prolactin gene. Result: All the birds were observed with the same genotype CC and the frequency of the C allele was one.


2021 ◽  
Author(s):  
Chiaki Horie ◽  
Chi Zhu ◽  
Kiyoshi Yamaguchi ◽  
Saya Nakagawa ◽  
Kiyoko Takane ◽  
...  

Abstract Aberrant activation of the Wnt/β-catenin signaling pathway plays a crucial role in the development and progression of colorectal cancer. Previously, we identified a set of candidate genes that were regulated by this signaling pathway, and we focused on MOSPD1, motile sperm domain containing 1, in this study. Immunohistochemical staining revealed that the expression of MOSPD1 was elevated in tumorous cells of colorectal cancer tissues compared with non-tumorous cells. Using ChIP-seq data and JASPAR database, we searched for the regulatory region(s) in the MOSPD1 gene as a target of the Wnt/β-catenin signaling, and identified a region containing three putative TCF-binding motifs in the 3’-flanking region. Additional analyses using reporter assay and ChIP-qPCR suggested that this region harbors an enhancer activity through an interaction with TCF7L2 and β-catenin. These data have clarified that MOSPD1 is a novel direct target of the Wnt/β-catenin signaling. In addition, the identification of its enhancer region may be helpful for the future studies of precise regulatory mechanisms of MOSPD1.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ana Cecília Guimarães Alves ◽  
Natalie Mary Sukow ◽  
Gabriel Adelman Cipolla ◽  
Marla Mendes ◽  
Thiago P. Leal ◽  
...  

In adulthood, the ability to digest lactose, the main sugar present in milk of mammals, is a phenotype (lactase persistence) observed in historically herder populations, mainly Northern Europeans, Eastern Africans, and Middle Eastern nomads. As the –13910∗T allele in the MCM6 gene is the most well-characterized allele responsible for the lactase persistence phenotype, the –13910C > T (rs4988235) polymorphism is commonly evaluated in lactase persistence studies. Lactase non-persistent adults may develop symptoms of lactose intolerance when consuming dairy products. In the Americas, there is no evidence of the consumption of these products until the arrival of Europeans. However, several American countries’ dietary guidelines recommend consuming dairy for adequate human nutrition and health promotion. Considering the extensive use of dairy and the complex ancestry of Pan-American admixed populations, we studied the distribution of –13910C > T lactase persistence genotypes and its flanking haplotypes of European origin in 7,428 individuals from several Pan-American admixed populations. We found that the –13910∗T allele frequency in Pan-American admixed populations is directly correlated with allele frequency of the European sources. Moreover, we did not observe any overrepresentation of European haplotypes in the –13910C > T flanking region, suggesting no selective pressure after admixture in the Americas. Finally, considering the dominant effect of the –13910∗T allele, our results indicate that Pan-American admixed populations are likely to have higher frequency of lactose intolerance, suggesting that general dietary guidelines deserve further evaluation across the continent.


Author(s):  
Frederik Friis Theisen ◽  
Lasse Staby ◽  
Frederik Grønbæk Tidemand ◽  
Charlotte O’Shea ◽  
Andreas Prestel ◽  
...  

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mingyue Cao ◽  
Lijun Shi ◽  
Peng Peng ◽  
Bo Han ◽  
Lin Liu ◽  
...  

Abstract Background Our previous genome-wide association study (GWAS) on milk fatty acid traits in Chinese Holstein cows revealed, the SNP, BTB-01556197, was significantly associated with C10:0 at genome-wide level (P = 0.0239). It was located in the down-stream of 5-hydroxytryptamine receptor 1B (HTR1B) gene that has been shown to play an important role in the regulation of fatty acid oxidation. Hence, we considered it as a promising candidate gene for milk fatty acids in dairy cattle. In this study, we aimed to investigate whether the HTR1B gene had significant genetic effects on milk fatty acid traits. Results We re-sequenced the entire coding region and 3000 bp of 5′ and 3′ flanking regions of HTR1B gene. A total of 13 SNPs was identified, containing one in 5′ flanking region, two in 5′ untranslated region (UTR), two in exon 1, five in 3′ UTR, and three in 3′ flanking region. By performing genotype-phenotype association analysis with SAS9.2 software, we observed that 13 SNPs were significantly associated with medium-chain saturated fatty acids such as C6:0, C8:0 and C10:0 (P < 0.0001 ~ 0.042). With Haploview 4.1 software, linkage disequilibrium (LD) analysis was performed. Two haplotype blocks formed by two and ten SNPs were observed. Haplotype-based association analysis indicated that both haplotype blocks were strongly associated with C6:0, C8:0 and C10:0 as well (P < 0.0001 ~ 0.0071). With regards to the missense mutation in exon 1 (g.17303383G > T) that reduced amino acid change from alanine to serine, we predicted that it altered the secondary structure of HTR1B protein with SOPMA. In addition, we predicted that three SNPs in promoter region, g.17307103A > T, g.17305206 T > G and g.17303761C > T, altered the binding sites of transcription factors (TFs) HMX2, PAX2, FOXP1ES, MIZ1, CUX2, DREAM, and PPAR-RXR by Genomatix. Of them, luciferase assay experiment further confirmed that the allele T of g.17307103A > T significantly increased the transcriptional activity of HTR1B gene than allele A (P = 0.0007). Conclusions In conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.


2021 ◽  
Author(s):  
Jianyu Gong ◽  
Jike Jiang ◽  
Jianwen Qu ◽  
Ju Li ◽  
Xin Chen ◽  
...  

Aim: To investigate the effect of rs3733846 in the flanking region of miR-143/145 on susceptibility to cervical squamous cell carcinoma (CSCC). Materials & methods: We collected venous blood samples from 242 CSCC patients and 250 healthy controls. The rs3733846 polymorphism was genotyped by SnaPshot and Sanger sequencing. The expression of miR-143/145 in CSCC tissues was detected by quantitative real-time PCR. Results: The rs3733846 AG genotype was associated with a decreased risk of CSCC in genetic model (AGvs.AA: adjusted odds ratio [OR]: 0.44; 95% CI: 0.30–0.66; p < 0.001). Patients with the rs3733846 AG/GG genotypes had a reduced risk of developing poorly differential status (OR: 0.57; 95% CI: 0.33–0.98; p < 0.04) and lymph node metastasis (OR: 0.49; 95% CI: 0.26–0.92; p < 0.03). Conclusion: The rs3733846 in the flanking region of miR-143/145 was related to the susceptibility of CSCC.


2021 ◽  
Author(s):  
Courtney L. Hall ◽  
Rupesh K. Kesharwani ◽  
Nicole R. Phillips ◽  
John V. Planz ◽  
Fritz J. Sedlazeck ◽  
...  

The high variability characteristic of short tandem repeat (STR) markers is harnessed for human identification in forensic genetic analyses. Despite the power and reliability of current typing techniques, sequence-level information both within and around STRs are masked in the length-based profiles generated. Forensic STR typing using next generation sequencing (NGS) has therefore gained attention as an alternative to traditional capillary electrophoresis (CE) approaches. In this proof-of-principle study, we evaluate the forensic applicability of the newest and smallest NGS platform available — the Oxford Nanopore Technologies (ONT) MinION device. Although nanopore sequencing on the handheld MinION offers numerous advantages, including on-site sample processing, the relatively high error rate and lack of forensic-specific analysis software has prevented accurate profiling across STR panels in previous studies. Here we present STRspy, a streamlined method capable of producing length- and sequence-based STR allele designations from noisy, long-read data. To demonstrate the capabilities of STRspy, seven reference samples (female: n = 2; male: n = 5) were amplified at 15 and 30 PCR cycles using the Promega PowerSeq 46GY System and sequenced on the ONT MinION device in triplicate. Basecalled reads were processed with STRspy using a custom database containing alleles reported in the STRSeq BioProject NIST 1036 dataset. Resultant STR allele designations and flanking region single nucleotide polymorphism (SNP) calls were compared to the manufacturer-validated genotypes for each sample. STRspy generated robust and reliable genotypes across all autosomal STR loci amplified with 30 PCR cycles, achieving 100% concordance based on both length and sequence. Furthermore, we were able to identify flanking region SNPs with >90% accuracy. These results demonstrate that nanopore sequencing platforms are capable of revealing additional variation in and around STR loci depending on read coverage. As the first long-read platform-specific method to successfully profile the entire panel of autosomal STRs amplified by a commercially available multiplex, STRspy significantly increases the feasibility of nanopore sequencing in forensic applications.


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