Haplotypic relationship between SNP and microsatellite markers at the NOS2A locus in two populations

Burgner, David; Rockett, Kirk A.; Ackerman, Hans; Hull, Jeremy; Usen, Stanley; Pinder, Margaret; Kwiatkowski, Dominic P.

doi:10.1038/sj.gene.6364022

Cited by 44 publications

(44 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As can be seen in Table 4, the frequencies of the rarer allele for these SNPs differ substantially between the two ethnic groups from Gambia and the United Kingdom and for SNPs À1026g/t and À1659c/t, the difference is significant (Burgner et al, 2003). Although not statistically significant, reduced MAFs for the three SNPs in the Norfolk population are indicative of a population with reduced genetic heterogeneity when compared to outbred populations.…”

Section: Resultsmentioning

confidence: 79%

“…The SNPs (À1026g/t, À1659c/t, À2447c/g) are clustered closely together in the proximal promoter region of the NOS2A gene and have been shown to be in complete and nearcomplete LD in the Gambian and UK samples, respectively (Burgner et al, 2003). The initial objective of this study was to determine the frequency, and assess LD, of these SNP alleles in an isolated population from Norfolk Island.…”

Section: Resultsmentioning

confidence: 99%

“…LD analysis NOS2A SNPs This study investigated three SNPs within the NOS2A gene located on chromosome 17q11.2-q12 that were previously identified and analyzed in a Gambian and UK Caucasian population (Burgner et al, 2003). The SNPs (À1026g/t, À1659c/t, À2447c/g) are clustered closely together in the proximal promoter region of the NOS2A gene and have been shown to be in complete and nearcomplete LD in the Gambian and UK samples, respectively (Burgner et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

“…The best candidate populations for detecting associations with common genetic variants are believed to be isolates with a small effective number of unrelated founders (10-100), as this offers the advantage of a smaller number of disease susceptibility variants within the test populations compared with outbred populations (Sheffield et al, 1998;Bourgain et al, 2000;Peltonen et al, 2000). Burgner et al (2003).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Linkage disequilibrium analysis in the genetically isolated Norfolk Island population

et al. 2007

Self Cite

View full text Add to dashboard Cite

Norfolk Island is a human genetic isolate, possessing unique population characteristics that could be utilized for complex disease gene localization. Our intention was to evaluate the extent and strength of linkage disequilibrium (LD) in the Norfolk isolate by investigating markers within Xq13.3 and the NOS2A gene encoding the inducible nitric oxide synthase. A total of six microsatellite markers spanning B11 Mb were assessed on chromosome Xq13.3 in a group of 56 men from Norfolk Island. Additionally, three single nucleotide polymorphisms (SNPs) localizing to the NOS2A gene were analyzed in a subset of the complex Norfolk pedigree. With the exception of two of the marker pairs, one of which is the most distantly spaced marker, all the Xq13.3 marker pairs were found to be in significant LD indicating that LD extends up to 9.5-11.5 Mb in the Norfolk Island population. Also, all SNPs studied showed significant LD in both Norfolk Islanders and Australian Caucasians, with two of the marker pairs in complete LD in the Norfolk population only. The Norfolk Island study population possesses a unique set of characteristics including founder effect, geographical isolation, exhaustive genealogical information and phenotypic data of use to cardiovascular disease risk traits. With LD extending up to 9.5-11 Mb, the Norfolk isolate should be a powerful resource for the localization of complex disease genes.

show abstract

Section: Resultsmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Linkage disequilibrium analysis in the genetically isolated Norfolk Island population

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, the presence of the shorter 12-repeat microsatellite allele, possibly downregulating the production of proinflammatory cytokines such as IL-1β in response to perinatal asphyxia, might explain the decreased risk of developing infant cerebral palsy in individuals that have short-form CCTTT microsatellite alleles. Since microsatellites are potentially unstable and of unknown functional relevance [32] the presence of some other yetnot-described mutation in the promoter region or the coding gene and -31 polymorphisms in the IL-1b gene increase it's transcription and 3 times the NO production, the haplotypes (CCTTT) 14 /-511T increase 6 or more times the NO production, conducing to massive neuronal dead by oxidative stress, this condition allows the PCI development like a sequel in children that suffered perinatal asphyxia.…”

Section: Discussionmentioning

confidence: 99%

Association of a Functional Inducible Nitric Oxide Synthase Promoter Variant with Susceptibility to Infantile Cerebral Palsy

HN¹

2015

J Neurol Disord

View full text Add to dashboard Cite

IntroductionThe hypoxic ischemic encephalopathy (HIE) secondary to perinatal asphyxia, affects a 1.5 to 5% of newborns; unfortunately 10% to 20% of infants with moderate HIE die and 30% to 40% develop neurological abnormalities, whilst 50% of infants with severe HIE, die and the remainder develop neurological conditions [1]. To our knowledge, the reason why some children that suffered perinatal asphysxia develop infant cerebral palsy while other children with similar clinical histories develop memory and learning difficulties but no motor disabilities remains unknown. Infantile cerebral palsy (ICP) is a neurological disease resulting from damage of the immature brain in newborn children, clinically it is a non-progressive brain insult that produces permanent and progressive secondary postural and movement disorders [2] and induces long-term complications such as muscle hypotrophy, deformities in the skull and spine [3]. In Mexico there are approximately 500,000 diagnosed cases of CP, be the leading cause of death in children from 5 to 14 years old [4] and it is the most common cause of physical disability in children throughout the world [5]. The main clinical spectrum of ICP includes quadriparesis, hemiparesis, and diparesis that affect upper and lower limbs to varying degrees. The therapeutic management of ICP is targeted at the lesions caused on the central nervous system, bone deformations and muscle hypotrophy [6]. The initial inflammatory response in the immature brain as a result of a traumatic birth can be mapped from proteins and metabolites that participate in inflammation and oxidative stress [7,8]. The main oxidative metabolite which is produced in the inflammatory response is the Nitric oxide (NO), it is a multifunctional molecule that has been Abstract Background: Recently it has been shown an increase in the interleukin 1 beta and nitrite levels in cerebrospinal fluid as a primary response of the immature brain to oxygen deprivation in newborns that suffered perinatal asphyxia, 30% to 40% of these patients later develop neurological abnormalities incluiding cerebral palsy. Formerly was shown that an increased enzyme activity of NOS2 is responsible for the increase in nitrite levels in cerebrospinal fluid. The NOS2A gene has a polymorphic microsatellite (CCTTT) n located at -2.6 Kb from the gene promoter. The expansion of this microsatellite to 13 or 14 repeats increases transcription of the NOS2A gene and triples the nitric oxide level under hypoglycemia and hypoxia conditions. The study aim was shown that the expansion of -2.6 Kb CCTTT microsatellite in the NOS2 gene promoter, constitutes a risk factor for developing cerebral palsy in newborns that suffered perinatal asphyxia

show abstract

Rapid Multiplexed Genotyping of Simple Tandem Repeats using Capture and High-Throughput Sequencing

et al. 2013

View full text Add to dashboard Cite

Although simple tandem repeats (STRs) comprise ~2% of the human genome and represent an important source of polymorphism, this class of variation remains understudied. We have developed a cost-effective strategy for performing targeted enrichment of STR regions that utilizes capture probes targeting the flanking sequences of STR loci, enabling specific capture of DNA fragments containing STRs for subsequent high-throughput sequencing. Utilizing a capture design targeting 6,243 STR loci <94bp and multiplexing eight individuals in a single Illumina HiSeq2000 sequencing lane we were able to call genotypes in at least one individual for 67.5% of the targeted STRs. We observed a strong relationship between (G+C) content and genotyping rate. STRs with moderate (G+C) content were recovered with >90% success rate, while only 12% of STRs with ≥80% (G+C) were genotyped in our assay. Analysis of a parent-offspring trio, complete hydatidiform mole samples, repeat analyses of the same individual, and Sanger sequencing-based validation indicated genotyping error rates between 7.6–12.4%. The majority of such errors were a single repeat unit at mono- or dinucleotide repeats. Altogether, our STR capture assay represents a cost-effective method that enables multiplexed genotyping of thousands of STR loci suitable for large scale population studies.

show abstract

Haplotypic relationship between SNP and microsatellite markers at the NOS2A locus in two populations

Cited by 44 publications

References 67 publications

Linkage disequilibrium analysis in the genetically isolated Norfolk Island population

Linkage disequilibrium analysis in the genetically isolated Norfolk Island population

Association of a Functional Inducible Nitric Oxide Synthase Promoter Variant with Susceptibility to Infantile Cerebral Palsy

Rapid Multiplexed Genotyping of Simple Tandem Repeats using Capture and High-Throughput Sequencing

Contact Info

Product

Resources

About