Haplotype analysis of human <i>AMPD1</i> gene: origin of common mutant allele
Bibliographic record
Abstract
yoadenylate deaminase is a skeletal muscle specific isoenzyme of AMP deaminase (AMPD; EC 3.5.4.6) that plays an important role in regulating adenylate energy charge and nucleotide metabolism.An inherited defect of this enzyme has been reported to be due to a single mutant allele with two linked mutations of C34T (exon 2, Q12X) and C143T (exon 3, P48L) of the AMPD1 gene in almost all cases. 1 2 Further, a previous report showed a very high frequency (10214%) of the C34T allele in whites and African Americans, 2 although it has not been found in a Japanese population.Although most individuals with homozygous C34T alleles are assumed to be asymptomatic, some have been reported to show a relatively mild clinical phenotype including exercise induced myalgia. 1 Recently, additional findings for missense mutations were reported in Japanese (R388W and R425H) 3 and in whites (G468T) 4 who showed muscle weakness and myalgia.Therefore, the relationship between abnormal purine nucleotide catabolism and skeletal muscle dysfunction 4 is intriguing.In addition, other studies have reported that the C34T allele correlates with improved clinical outcome in patients with heart disease.5 6 We speculated that reduced AMPD activity in skeletal muscle would increase the production of the cardioprotection molecule, adenosine, resulting in increased levels of adenosine in the circulating system, although the fundamental mechanisms responsible for the disorder due to AMPD mutations are unclear.In the present study, we attempted to determine other AMPD1 mutations and their distribution in ethnically diverse population groups, in order to better understand AMPD1 deficiency and its functional relevance.We identified 35 variations in and around the AMPD1 locus, including newly identified missense mutations.By estimating SNP haplotypes and defining typical haplotypes of the AMPD1 locus, we were also able to describe a phylogenic tree for ancestral AMPD1 haplotypes responsible for the most common variant, C34T.Furthermore, we identified two new mutant alleles, A860T (K287I) and G930T (M310I), in German myopathic patients and revealed their enzymatic defect.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".