Single Nucleotide Polymorphisms (SNPs)

Introduction:
Drug transporters are key determinants of pharmacokinetic and pharmacodynamic profiles of certain drugs. SLC47A1 (MATE1) and SLC47A2 (MATE2) are major efflux transporters involved in the hepatic and renal excretion of many cationic drugs including metformin. Our study was proposed to determine the normative frequencies of the single nucleotide polymorphisms (SNPs) rs2289669 and rs12943590 in the SLC47A1 and SLC47A2 genes, respectively, in South Indian population and also to compare those with those of the HapMap populations.
Methods:
One hundred two unrelated healthy volunteers from South India were enrolled in the study. Genomic DNA was extracted by ‘phenol-chloroform extraction method’ from the peripheral blood leucocytes and genotyping was accomplished by real-time polymerase chain reaction using TaqMan SNP genotyping assay method.
Results:
In contrast to other populations, the minor allele in SLC47A1 gene was found to be “G” with a frequency of 46.6% in South Indian population. The populations of Hans Chinese in Beijing (HCB) [P = 0.017] and Japanese in Tokyo (JPT) [P < 0.001] had significantly different genotype
and allele frequencies (SNP rs2289669) compared to those of South Indian population. Similarly, in the SNP rs12943590 of SLC47A2 gene, the genotype and allele frequencies of South Indian population differed significantly from those of Yoruba in Ibadan, Nigeria (YRI) [P < 0.001] and
Utah residents with Northern and Western European ancestry (CEU) [P = 0.005] populations.
Conclusion:
Thus, the allele and genotype distributions of SLC47A1 and SLC47A2 gene polymorphisms were established in South Indian population and were found to be different from the frequencies of other ethnicities.

The VHL tumour suppressor gene codes for von-Hippel Lindau (VHL)
protein which acts by association with Elongin C and Hypoxia Inducing Factor-1
alpha (HIF). Two functional sub-domains in the protein model of VHL contain binding
sites for these proteins. Alpha domain of VHL protein contains the binding site for
Elongin C (tumorigenic cluster A) whereas; the beta domain contains the binding site
for HIF-1 alpha (tumorigenic cluster B). The complex formation between VHL, Elongin
C and HIF- 1 alpha protein is crucial for the regulation of ubiquitin dependent
proteolysis of oncogenic proteins. Henceforth defects in the complex formation may
lead to von-Hippel Lindau disease. A majority of VHL disease causing mutations
found to occur in these binding sites are highly conserved. In this computational analysis,
we predicted the functional effect of Single amino acid Polymorphisms (SAPs)
in VHL-interacting proteins with the aid of pathogenicity and protein stability predictors.
Furthermore, molecular dynamic behavior of the native and mutant protein complexes
were analyzed by using different parameters such as Root Mean Square Deviation,
Root Mean Square Fluctuation and Hydrogen bonding variations Molecular
dynamics studies were performed for five variants S111R, H115Q and W117C,
L158V and C162F of VHL protein that occur in the Elongin-C and HIF-1 alpha protein
binding domain. Through the molecular dynamics simulations analysis, we observed
that the stability and flexibility between VHL-Elongin-C and VHL-HIF-1
complexes were altered. Our strategy may be valuable for understanding SAP effects
on protein-protein interactions with function and their role in human genetic diseases,
linking structure function relationship and also for the development of novel pharmacological
strategies.

The susceptibility to various diseases is studied with association to genetic polymorphisms. Among these polymorphisms, single‑nucleotide polymorphisms (SNPs) are very common throughout the genome. The recent advances in genetic assay techniques and increase in SNP databases are paving a way for investigation of susceptibility genes for periodontitis. This article attempts to review the role of SNP and its implications in periodontal disease and management.

Guillain-Barré syndrome (GBS) is an acute inflammatory
demyelinating polyneuropathy, usually a post-infectious
autoimmune-mediated disorder of the peripheral nervous
system. Tumor necrosis factor-α (TNF-α) is one of the major
pro-inflammatory cytokines that may affect pathogenesis of
GBS. A definite role of TNF-polymorphism in the
pathogenesis of GBS is largely unknown; very few data are
available from developing countries. We aimed to investigate
polymorphisms in the promoter region of TNF-α gene in GBS
patients and healthy controls to assess their association for
GBS pathogenesis and disease outcome. In this study, we
performed a prospective study among 300 GBS patients,
enrolled from Dhaka Medical College Hospital and 300
healthy controls. TNF-α (-238G/A, -308G/A, -857C/T, and -
863C/A) polymorphisms were detected by polymerase chain
reaction-restriction fragment length polymorphism (PCRRFLP)
and allele specific-PCR. TNF-α -863C/A polymorphism
was significantly associated with GBS patients compared with
healthy controls. CA heterozygote of TNF-α -863 increased
the susceptibility of GBS patients compared with controls (P
<0.05, OR=1.5, 95% CI=1.1-2.2). TNF-α -863 AA mutant
genotype was significantly associated with LOS positive
patients compared with LOS negative patients (P<0.05,
OR=15.2, 95% CI=0.9-263.7). In addition, A allele of TNF-α
-863 was significantly associated with disease severity
(P<0.05, OR=1.8, 95% CI=1.1-2.8). However, TNF-α -238
G/A, -308 G/A and -857 C/T were not associated with GBS
pathogenesis and disease outcome. In conclusion, TNF-α -
863 A allele might play an important role for the severity and
pathogenesis of GBS in the Bangladeshi population, however,
further studies are required to confirm this study from
developed and low-income countries.

Guillain-Barr ´e syndrome (GBS) is a post-infectious
immune-mediated polyneuropathy. Complement activation
plays a crucial role in the induction and extent of the postinfectious
immune-mediated peripheral nerve damage in
GBS patients. Mannose-binding lectin (MBL) activates the
complement system via the lectin pathway after recognition
of repetitive sugar moiety on pathogens. We aimed to
investigate whether MBL2 genotype and serum MBL level
are associated with the development and severity of GBS
in Bangladeshi population. In this study, we determined
the polymorphisms in the promoter region and exon1 of
the MBL2 gene in 322 GBS patients and 320 healthy
controls using high throughput melt curve genotyping by
real time PCR. GBS patients had significant higher frequency
of the HH genotype, HY haplotype, and HYA haplotype
compared with healthy controls (p<0.004). Two H-alleles or
HYA genotype also increased risk of developing GBS two
to three times higher than one H-allele or HYA genotypes,
respectively. The frequencies of HH and HYA genotypes
were significantly associated with disease severity (p<0.05).
HY genotypes were also found associated with increased risk
of developing GBS (p<0.002). No significant distribution was
observed in exon1 polymorphism between GBS patients and controls. However, A/A haplotype in exon1 was
significantly associated with functional disability (F-score) at
entry (p<0.05). High serum concentration of MBL was found
among severely affected (MRC-sumscore <40) GBS patients
compared to mildly affected patients (MRC-sumscore ≥40).
Presence of anti-GM1 antibody was significantly associated
with high serum concentration of MBL in GBS patients
(p<0.05). No significant association was found in different
subtypes of GBS regarding MBL gene polymorphisms. In
conclusion, our study suggests an association between
MBL2 gene polymorphisms and severity of GBS in
Bangladesh. MBL2 gene polymorphisms related to high
production of MBL may induce more nerve damage and
clinical deficits in GBS patients

Background and Aim: Bali Cattle (Bos j. javanicus) is a local breed originating in Indonesia, accounting for 32.3% of the total cattle population. To date, no studies of the genetic structure and demographic status of Bali cattle have been conducted, even though the breeding of Bali cattle has a long and unique history that is likely to have impacted its genetic diversity. Therefore, a study that used molecular breeding technologies to characterize the demography of Bali cattle would be timely. This study aimed to examine genome diversity in Bali cattle and estimate the linkage disequilibrium (LD) and effective population size (Ne) values in the cattle population.

Materials and Methods: In this study, we explored the population structure and genetic diversity of Bali cattle using genomic-level analyses. Our study primarily studied cattle that had been bred in livestock breeding centers since these breeds had subsequently spread throughout Indonesia. We focused on characterizing the genetic structure, determining the level of LD present, and estimating the Ne of the Bali cattle population. The genomic data used for this study were obtained from DNA samples of 48 Bali cattle collected at the Breeding Center of Bali Cattle as well as 54 genomic samples from Bali cattle collected elsewhere in Indonesia that had been used in recent publications. This genomic dataset included exclusively 50K single nucleotide polymorphisms (SNP) array (Illumina Bovine 50SNP bead chip, Illumina, USA) data.

Results: We found that the LD values of Bali cattle from the breeding center and those raised elsewhere were 0.48±0.43 and 0.39±0.40, respectively. Subsequently, the Ne value of Bali cattle from the breeding center and farmers was 151 and 96, respectively.

Conclusion: Our results suggest that the selection program of the breeding center is beneficial for maintaining the genetic diversity of Bali cattle.

Las variedades de cacao fino o de aroma en el Perú son utilizados para elaborar los mejores chocolates del mundo por sus exquisitas y poco comunes características organolépticas, Estas características permiten que el cacao peruano gane reconocimiento internacional y de ahí su gran valor económico. A pesar de esto,
poco se sabe sobre los componentes genéticos y/o ambientales que contribuyen a la exclusividad de este valioso recurso económico. En el proyecto de investigación aplicada: “Estudio molecular de la diversidad genética de los cacaos aromáticos en el Perú con fines del fortalecimiento de su competitividad y aumento de la producción nacional de cacao de calidad”, financiado por Innóvate Perú del Ministerio de la
Producción, se tiene como objetivos determinar la variabilidad genética y caracterización organoléptica de más de 100 tipos de cacao fino o de aroma que se cultivan a lo largo de las cinco principales regiones del Perú (Amazonas, Cusco, San Martin, Piura y Huánuco). Adicionalmente, la Universidad Nacional Agraria de la Selva en Tingo María y el Instituto de Investigaciones de la Amazonia Peruana en Tarapoto,
hospedarán bancos de germoplasma y de propagación de esquejes para la difusión y estudios de estos valiosos recursos. Hasta inicios del 2017, ya se han recolectado más de 80 genotipos provenientes de las cinco regiones. Protocolos para análisis sensoriales que cumplan los más rigurosos estándares internacionales se han venido estableciendo. Por otro lado, técnicas de marcadores moleculares usando marcadores de DNA tipo SSR y SNPs, seguido por secuenciamiento de ADN, se vienen estableciendo. Estudios de asociación de fenotipo-genotipo formarán parte del conocimiento generado en este proyecto. Adicionalmente, estos conocimientos permitirán generar información genómica valiosa para salvaguardar nuestra biodiversidad nativa, otorgándole a los productores y sus asociaciones de herramientas para proteger sus recursos genéticos y a los potenciales mejoradores de cacao más luces en cuanto a la asociación genotipo-calidad. Se espera que a fin del proyecto, se cuente con los resultados de genotipificación de más de 100 genotipos de cacao fino o de aroma y mediante el resecuenciamiento se revelen SNPs particulares para cada grupo genético en cada región muestreada.

Complement activation plays a crucial role in the pathogenesis
of Guillain-Barré syndrome (GBS), especially in
pathogen recognition and nerve damage. Previous studies
indicated that severity in GBS is associated with genetic
polymorphisms of mannose binding lectin (MBL). This pattern
recognition receptor of the innate immune system binds
to repetitive sugar moieties on both pathogens and apoptotic
cells leading to complement activation via the lectin
pathway and subsequent killing or clearance. We aimed to
confirm if MBL2 genotypes and MBL levels are associated
with the GBS susceptibility and severity in patients from Bangladesh and conducted a meta-analysis. Polymorphisms
in the promoter region and exon 1 of the MBL2 gene was
determined in 322 GBS patients and 320 healthy controls
using high throughput melt curve genotyping by real time
PCR. GBS patients had significant higher frequency of the
HH genotype, HY haplotype, and HYA haplotype compared
to healthy controls (p<0.004). Two H-alleles or two HYA
haplotypes compared to a single H-allele or HYA haplotype
further increased the risk of developing GBS. H-alleles and
HYA haplotypes were associated with more severe GBS
(MRC-sumscore <40) (p<0.05). HY genotypes were also
found associated with increased risk of developing GBS
(p<0.002). The frequency of the H-allele, the HY promoter
haplotype and the HYA haplotype were all associated with
an increased MBL production. Serum levels of MBL were
higher in severely affected patients compared to mildly
affected patients (P<0.001). Presence of anti-GM1 antibody
was also associated with high serum concentration of MBL
(p<0.05). MBL2 gene polymorphisms were not associated
with the presence of axonal or demyelinating subtypes of
GBS. Meta-analysis of the combined Dutch and Bangladeshi
dataset including 591 GBS patients and 530 healthy controls
revealed that HYA-allele and H-allele were associated with
the occurrence and severity of GBS. HYA-allele and H-allele
was associated with high level of MBL production in both
studies. In conclusion, MBL2 gene polymorphisms related to
high levels of serum MBL are associated with disease susceptibility and severity in GBS.

Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD)

یکی از نیازهای اساسی برای ساخت مدل در علومی مانند بیوانفورماتیک، استفاده از روش های انتخاب ویژگی می باشد. دلیل این امر، بالا بودن ابعاد داده ها در علوم مختلف بیوانفورماتیک مثل انتخاب SNPها می باشد. بنابراین، استفاده از روش های کاهش ابعاد اجتناب ناپذیر شده است. در این مقاله ما از یک روش ترکیبی جهت انتخاب SNPهای مهم موجود در یک مجموعه از بانک های اطلاعاتی استفاده کرده ایم. SNPها اطلاعات مفیدی را جهت تشخیص ژن های مرتبط با بیماری های دارای مکانیسم توارثی پیچیده مثل انواع سرطان، دیابت، بیماری های عروقی و برخی انواع بیماری های ذهنی فراهم می-کنند. در روش پیشنهادی ما، ابتدا الگوریتم انتخاب ویژگیِ مبتنی بر همبستگی اجرا می شود و تعداد کمتری از ویژگی های ورودی را انتخاب می کند. سپس این ویژگی ها به عنوان ورودی مرحله دوم، یعنی الگوریتم k-نزدیک ترین همسایه استفاده می شوند. ویژگی های انتخاب شده نهایی، در واقع مهم ترین SNPهای موجود در بانک اطلاعاتی می باشند. نتایج حاصله نشان دهنده قدرت کاهش ابعاد و دقت قابل قبول الگوریتم پیشنهادی در تشخیص SNPهای مهم می باشد.

Copy number variations (CNVs) are an important source of genomic structural variation, and can be used as markers to investigate phenotypic and economic traits. CNVs also have functional effects on gene expression and can contribute to disease susceptibility in mammals. Currently, single nucleotide polymorphism genotyping arrays (SNP chips) are the technology of choice for identifying CNV variations. Microarray technologies have recently been used to study the bovine genome. The objective of the present study was to develop CNVs in Holstein cows from the Northwest of Mexico using the Affymetrix Axiom Genome-Wide BOS 1 Array, which assays 648,315 SNPs and provides a wide coverage for

Cytosolic pattern recognition receptors play key roles in innate immune response. Nucleotide binding and oligomerisation domain containing protein 1 (NOD1) belonging to the Nod-like receptor C (NLRC) sub-family of Nod-like receptors (NLRs) is important for detection and clearance of intra-cellular Gram negative bacteria. NOD1 is involved in activation of pro-inflammatory pathways. Limited structural data is available for NOD1. Using different templates for each domain of NOD1, we determined the full-length homology model of NOD1. ADP binding amino acids within the nucleotide binding domain (NBD) of NOD1 were also predicted. Key residues in inter-domain interaction were identified by sequence comparison with Oryctolagus cuniculus NOD2, a related protein. Interactions between NBD and winged helix domain (WHD) were found to be conserved in NOD1. Functional and structural effect of single nucleotide polymorphisms within the NOD1 NBD domain associated with susceptibility risk to Ulcerative colitis (UC), an inflammatory disorder of the colon was evaluated by in silico studies. Mutations W219R and L349P were predicted to be damaging and disease associated by prediction programs SIFT, PolyPhen2, PANTHER, SNP&GO, PhD SNP and SNAP2. We further validated the effect of W219R and L349P mutation on NOD1 function in vitro. Elevated mRNA expression of pro-inflammatory cytokines IL8 and IL-1β was seen as compared to the wild type NOD1 in intestinal epithelial cell line HT29 when stimulated with NOD1 ligand. Thus, these mutations may indeed have a bearing on pathogenesis of inflammation during UC.