Targeted gene walking by low stringency polymerase chain reaction: assignment of a putative human brain sodium channel gene (SCN3A) to chromosome 2q24-31.

Malo, Madhu S.; Srivastava, Kalpana; Andresen, J. Michael; Chen, Xiao Ning; Korenberg, Julie R.; Ingram, Vernon M.

doi:10.1073/pnas.91.8.2975

Cited by 35 publications

(14 citation statements)

References 28 publications

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“…SCN3A encodes the alpha subunit of the voltage-gated sodium channel. Sodium channels mediate the voltage-dependent permeability of excitable membranes to sodium ions, facilitating the generation and propagation of action potentials in neurons (Malo et al, 1994). The HADH protein is one of the enzymes in the fatty acid beta-oxidation pathway, which catalyzes the conversion of 3-hydroxyacyl-CoA to 3-oxoacyl-CoA, a key step in fatty acid metabolism during brain development (Reichmann et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Gene Network Effects on Brain Microstructure and Intellectual Performance Identified in 472 Twins

Chiang¹,

Barysheva²,

McMahon³

et al. 2012

Journal of Neuroscience

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A major challenge in neuroscience is finding which genes affect brain integrity, connectivity, and intellectual function. Discovering influential genes holds vast promise for neuroscience, but typical genome-wide searches assess around one million genetic variants one-by-one, leading to intractable false positive rates, even with vast samples of subjects. Even more intractable is the question of which genes interact and how they work together to affect brain connectivity. Here we report a novel approach that discovers which genes contribute to brain wiring and fiber integrity at all pairs of points in a brain scan. We studied genetic correlations between thousands of points in human brain images from 472 twins and their non-twin siblings (mean age: 23.7±2.1 SD years; 193 M/279 F). We combined clustering with genome-wide scanning to find brain systems with common genetic determination. We then filtered the image in a new way to boost power to find causal genes. Using network analysis, we found a network of genes that affect brain wiring in healthy young adults. Our new strategy makes it more computationally tractable to discover genes that affect brain integrity. The gene network showed small-world and scale-free topologies, suggesting efficiency in genetic interactions, and resilience to network disruption. Genetic variants at hubs of the network influence intellectual performance by modulating associations between performance intelligence quotient (IQ) and the integrity of major white matter tracts, such as the callosal genu and splenium, cingulum, optic radiations, and the superior longitudinal fasciculus.

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Section: Discussionmentioning

confidence: 99%

Gene Network Effects on Brain Microstructure and Intellectual Performance Identified in 472 Twins

Chiang¹,

Barysheva²,

McMahon³

et al. 2012

Journal of Neuroscience

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“…Several genes in the linked region of chromosome 2q21-q33 encode proteins implicated in the regulation of action potentials in the brain: SCN1A on 2q24, SCN2A1 on 2q23, SCN2A2 on 2q23-q24, and SCN3A on 2q24-q31. All four encode isoforms of a brain sodium-channel a-subunit (Han et al 1991;Lu et al 1992;Malo et al 1994aMalo et al , 1994b. Sodium channels isolated from vertebrate brain contain a large (230-270 kD) transmembrane a-subunit and one or two smaller (33-38 kD) b-subunits (Auld et al 1988).…”

Section: Discussionmentioning

confidence: 99%

A Second Locus for Familial Generalized Epilepsy with Febrile Seizures Plus Maps to Chromosome 2q21-q33

Baulac

Gourfinkel‐An

Picard

et al. 1999

The American Journal of Human Genetics

184

107

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We report a clinical and genetic study of a family with a phenotype resembling generalized epilepsy with febrile seizures plus (GEFS+), described by Berkovic and colleagues. Patients express a very variable phenotype combining febrile seizures, generalized seizures often precipitated by fever at age >6 years, and partial seizures, with a variable degree of severity. Linkage analysis has excluded both the beta 1 subunit gene (SCN1B) of a voltage-gated sodium (Na+) channel responsible for GEFS+ and the two loci, FEB1 and FEB2, previously implicated in febrile seizures. A genomewide search, under the assumption of incomplete penetrance at 85% and a phenocopy rate of 5%, permitted identification of a new locus on chromosome 2q21-q33. The maximum pairwise LOD score was 3.00 at recombination fraction 0 for marker D2S2330. Haplotype reconstruction defined a large (22-cM) candidate interval flanked by markers D2S156 and D2S2314. Four genes coding for different isoforms of the alpha-subunit voltage-gated sodium channels (SCN1A, SCN2A1, SCN2A2, and SCN3A) located in this region are strong candidates for the disease gene.

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“…In the hemidegenerate PCR approach, specific PCR primers were used together with degenerate A-domain PCR primers (MTF2 and MTF; Neilan et al, 1999). For amplification of flanking regions, we performed PCR using a single, specific primer and a low annealing temperature (Malo et al, 1994). This approach successfully generated a series of overlapping fragments.…”

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confidence: 99%

Structural analysis of a non-ribosomal halogenated cyclic peptide and its putative operon from Microcystis: implications for evolution of cyanopeptolins

et al. 2007

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The structure of the major peptide produced by Microcystis cf. wesenbergii NIVA-CYA 172/5, the halogenated heptapeptide cyanopeptolin-984, was determined using LC/MS/MS. A gene cluster encoding a peptide synthetase putatively producing a cyanopeptolin was cloned from the same strain and sequenced. The cluster consists of four genes encoding peptide synthetases and one gene encoding a halogenase. Two additional ORFs transcribed in the opposite direction were found in the 59 flanking sequence; one of these encodes an ABC transporter. The overall organization of the cyanopeptolin synthetase operon (mcn) resembles a previously analysed anabaenopeptilide synthetase operon (apd) from Anabaena strain 90. Phylogenetic analyses of the individual domains from Mcn, Apd and other cyanobacterial peptide synthetases showed clustering of the adenylation domains according to function irrespective of operon origin -indicating strong functional constraints across peptide synthetases. In contrast, the condensation and thiolation domains to a large extent grouped according to operon affiliation or position in the respective operons. Phylogenetic analyses of condensation domains indicated that N-terminal domains and domains that condense L-amino acids and D-amino acids, respectively, form three separate groups. Although recombination events are likely to be involved in the evolution of mcn, no clear evidence of genetic recombination between the two cyanopeptolin gene clusters was found. Within the genus Microcystis, microcystin and cyanopeptolin synthetases have an evolutionary history of genomic coexistence. However, the data indicated that the two classes of peptide synthetase gene clusters have evolved independently.

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Targeted gene walking by low stringency polymerase chain reaction: assignment of a putative human brain sodium channel gene (SCN3A) to chromosome 2q24-31.

Cited by 35 publications

References 28 publications

Gene Network Effects on Brain Microstructure and Intellectual Performance Identified in 472 Twins

Gene Network Effects on Brain Microstructure and Intellectual Performance Identified in 472 Twins

A Second Locus for Familial Generalized Epilepsy with Febrile Seizures Plus Maps to Chromosome 2q21-q33

Structural analysis of a non-ribosomal halogenated cyclic peptide and its putative operon from Microcystis: implications for evolution of cyanopeptolins

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