Bardet-Biedl syndrome in Newfoundland : molecular genetics of a rare recessive disorder in a small isolated population
Bibliographic record
Abstract
Bardet-Biedl syndrome (BBS) is characterized by retinal dystrophy, dysmorphicextremities, renal structural abnormalities, obesity, and hypogenitalism in males. This autosomal recessive disorder is genetically heterogenous with four identified loci, BBS1-4 (11q, 16q, 3p and 15q respectively). BBS is a relatively rare disorder, but it is approximately ten times more prevalent in Newfoundland than in northern European populations. -- To investigate the high incidence of BBS in the Newfoundland population, members of 17 BBS families were analyzed by haplotype and linkage analyses. Initially, linkage of five families to BBS1 one each to BBS2 and BBS3 and exclusion of six families from the four known BBS loci was observed. -- A large consanguineous Newfoundland BBS family, excluded from the four known BBS loci, was used to identify a fifth BBS gene locus (BBS5) on 2q31 in a genome-wide scan. However, this gene did not segregate in any other of the five unlinked families. Therefore, another genome scan was implemented on a consanguineous family excluded from the five BBS loci. Evidence of a sixth BBS gene (BBS6) on 20p12 was established and the critical interval narrowed to 2 cM using five other unlinked families. Located within this region is a putative chaperonin gene (MKKS) involved in McKusick-Kaufman syndrome, a disorder with an overlapping phenotype with BBS. When MKKS was screened for mutations in six Newfoundland BBS families, one missense and two frameshift mutations were identified. Thus, MKKS was the first gene identified to cause BBS. Remarkably, one family could be excluded from all six BBS loci, indicating the existence of a seventh BBS gene (BBS7). -- By mutational and/or haplotype and linkage analyses, it was possible to assign 14 of the 17 Newfoundland BBS families to known BBS loci. Six families had mutations in MKKS/BBS6, five families were associated with the BBS1 locus, and one family to each of the BBS2, BBS3 and BBS5 loci. Additionally, one family was excluded from the six known BBS loci. The discovery of MKKS/BBS6 should aid in the ascertainment of other BBS genes and contribute to the basic understanding of the manifestations of BBS.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".