Molecular cloning of cDNAs encoding rat and human medium-chain acyl-CoA dehydrogenase and assignment of the gene to human chromosome 1.

Matsubara, Yoichi; Kraus, Jan P.; Yang‐Feng, Teresa L.; Francke, Uta; Rosenberg, León E.; Tanaka, Kay

doi:10.1073/pnas.83.17.6543

Cited by 62 publications

(28 citation statements)

References 36 publications

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“…The foods most commonly eaten by GSM (such as Usnea diffracta Vain., leaves from Rosaceae and tree bark) are high-fiber, low-energy nutritional sources, and it therefore seems reasonable to hypothesize that leaf-eating monkeys living in high-altitude forests should employ enhanced energy metabolism to efficiently absorb and exploit scarce nutrients. For example, ACADM and HADNB encode the enzymes involved in catalyzing the initial and final reactions in the β-oxidation of fatty acids 12,13 . ALDH3A2, a typical fatty aldehyde dehydrogenase, catalyzes oxidation of the long-chain aldehydes produced by lipid metabolism.…”

Section: Pgk Tpi1mentioning

confidence: 99%

Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history

et al. 2014

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Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146× coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30× coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.Knowledge of the patterns and processes underlying the evolution of alternative dietary strategies in nonhuman primates is critical to understanding hominin evolution, nutritional ecology and applications in biomedicine 1 . Colobines, a group of Old World monkeys, serve as an important model organism for studying the evolution of the primate diet because of their adaptation to folivory: they primarily eat leaves and seeds rather than fruits and insects as their major food source. In their specialized and compartmentalized stomachs, colobines allow symbiotic bacteria in the foregut to ferment structural carbohydrates and then recover nutrients by digesting the bacteria 2 . This strategy is similar to that used by other foregut fermenters found in an evolutionarily distantly related group of mammals (for example, artiodactyls). Although a number of primate genomes have been sequenced thus far, high-quality genome sequence information is absent for Asian and African colobines, a key group for elucidating the evolution and adaptation of primates as a whole. Snub-nosed monkeys (Rhinopithecus species) are a group of endangered colobines, which were once widely distributed in Asia but are now limited to mountain forests in China and Vietnam 3 (Supplementary Fig. 1).The golden snub-nosed monkey (GSM, R. roxellana) is recognized as an iconic endangered species in China for its golden coat, blue facial coloration, snub nose and specialized life history. Among its congeners, the black-white snub-nosed monkey (R. bieti), endemic to the Tibetan plateau, has the highest altitudinal distribution (>4,000 m above sea level) of any nonhuman primate. Given the above features and the fact that Rhinopithecus species consume difficult-to-digest foods that contain tannins (for example, leaves and pine seeds), we expected to identify genetic adaptations that enhance the breakdown of toxins, improve the regulation of energy metabolism and facilitate the digestion of symbiotic microbacteria. RESULTS Genomic sequences and the accumulation of...

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Section: Pgk Tpi1mentioning

confidence: 99%

Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history

et al. 2014

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“…The human MCAD gene has been localized to the short arm of chromosome 1, at Ip31, locus ACADM (Matsubara et al 1986). Because obligate heterozygous parents of patients suffering from MCAD deficiency are known not to have symptoms, MCAD deficiency can be considered as an autosomal recessive disorder.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: identification of a lys329 to glu mutation in the MCAD gene, and expression of inactive mutant enzyme protein in E. coli

et al. 1991

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Summary. A series of experiments has established the molecular defect in the medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) gene in a family with MCAD deficiency. Demonstration of intra-mitochon drial mature MCAD indistinguishable in size (42.5-kDa) from control MCAD, and of mRNA with the correct size of 2.4 kb, indicated a point-mutation in the coding region of the MCAD gene to be disease-causing. Con sequently, cloning and DNA sequencing of polymerase chain reaction (PCR) amplified complementary DNA (cDNA) from messenger RNA of fibroblasts from the patient and family members were performed. All clones sequenced from the patient exhibited a single base sub _titution from adenine (A) to guanine (G) at position ~85 in the MCAD cDNA as the only consistent base-var iation compared with control cDNA. In contrast, the parents contained cDNA with the normal and the mu tated sequence, revealing their obligate carrier status. Allelic homozygosity in the patient and heterozygosity for the mutation in the parents were established by a modified PCR reaction, introducing a cleavage site for the restriction endonuclease NcoI into amplified geno mic DNA containing G 985 . The same assay consistently revealed A 985 in genomic DNA from 26 control individu als. The A to G mutation was introduced into an E. coli expression vector producing mutant MCAD, which was demonstrated to be inactive, probably because of the in ability to form active tetrameric MCAD. All the experi ments are consistent with the contention that the G 985 mutation, resulting in a lysine to glutamate shift at posi tion 329 in the MCAD polypeptide chain, is the genetic cause of MCAD deficiency in this family. We found the Offprint requests to: N. Gregersen.

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“…54 ACADM gene consists of 12 exons that encode 421 amino acids. 55 The use of NBS for early detection of MCAD deficiency has revealed a more varied mutational and biochemical spectrum of MCAD deficiency than the studies done on clinically ascertained populations.…”

Section: Molecular Aspectsmentioning

confidence: 99%

Screening for medium-chain acyl CoA dehydrogenase deficiency: current perspectives

Soler‐Alfonso¹,

Bennett²,

Fıçıcıoğlu³

2016

RRN

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Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder associated with fatty acid oxidation. The disorder is characterized by inability to generate sufficient energy from fatty acid metabolism during periods of catabolic stress caused by intercurrent illness or prolonged fasting. The metabolic consequences are severe and include hypoketotic hypoglycemia leading to a Reye-like hepatic encephalopathy syndrome and sudden death. If individuals are detected before a life-threatening episode, the complications of MCAD deficiency are preventable. Newborn metabolic screening enables the early detection of MCAD deficiency in many countries worldwide. The metabolic marker for MCAD deficiency "octanoylcarnitine" (C8) can be detected with a high degree of sensitivity in the newborns by tandem mass spectrometry. The 985A.G (K329E) mutation accounts for the majority of disease alleles, and approximately 47%-80% of MCAD patients are homozygotes for this mutation. Newborns homozygous for the 985A.G mutation have higher octanoylcarnitine levels than those who are heterozygous for 985A.G mutation or possess other genotypes. Time of sampling after birth and prematurity may affect the octanoylcarnitine levels in MCAD-deficient newborns. Tandem mass spectrometry newborn blood spot screening for MCAD deficiency is accurate and effective, and reduces morbidity and mortality in affected children.

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Molecular cloning of cDNAs encoding rat and human medium-chain acyl-CoA dehydrogenase and assignment of the gene to human chromosome 1.

Cited by 62 publications

References 36 publications

Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history

Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history

Molecular characterization of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: identification of a lys329 to glu mutation in the MCAD gene, and expression of inactive mutant enzyme protein in E. coli

Screening for medium-chain acyl CoA dehydrogenase deficiency: current perspectives

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