scispace - formally typeset
Search or ask a question
JournalISSN: 0964-6906

Human Molecular Genetics 

Oxford University Press
About: Human Molecular Genetics is an academic journal published by Oxford University Press. The journal publishes majorly in the area(s): Gene & Mutation. It has an ISSN identifier of 0964-6906. Over the lifetime, 12220 publications have been published receiving 1058685 citations. The journal is also known as: Hum Mol Genet.


Papers
More filters
Journal ArticleDOI
TL;DR: RNAs appear to comprise a hidden layer of internal signals that control various levels of gene expression in physiology and development, including chromatin architecture/epigenetic memory, transcription, RNA splicing, editing, translation and turnover.
Abstract: The term non-coding RNA (ncRNA) is commonly employed for RNA that does not encode a protein, but this does not mean that such RNAs do not contain information nor have function. Although it has been generally assumed that most genetic information is transacted by proteins, recent evidence suggests that the majority of the genomes of mammals and other complex organisms is in fact transcribed into ncRNAs, many of which are alternatively spliced and/or processed into smaller products. These ncRNAs include microRNAs and snoRNAs (many if not most of which remain to be identified), as well as likely other classes of yet-to-be-discovered small regulatory RNAs, and tens of thousands of longer transcripts (including complex patterns of interlacing and overlapping sense and antisense transcripts), most of whose functions are unknown. These RNAs (including those derived from introns) appear to comprise a hidden layer of internal signals that control various levels of gene expression in physiology and development, including chromatin architecture/epigenetic memory, transcription, RNA splicing, editing, translation and turnover. RNA regulatory networks may determine most of our complex characteristics, play a significant role in disease and constitute an unexplored world of genetic variation both within and between species.

2,204 citations

Journal ArticleDOI
TL;DR: The biological significance of 5-methylcytosine was in doubt for many years, but is no longer, and it has become clear that programmed changes in methylation patterns are less important in the regulation of mammalian development than was previously believed.
Abstract: The biological significance of 5-methylcytosine was in doubt for many years, but is no longer. Through targeted mutagenesis in mice it has been learnt that every protein shown by biochemical tests to be involved in the establishment, maintenance or interpretation of genomic methylation patterns is encoded by an essential gene. A human genetic disorder (ICF syndrome) has recently been shown to be caused by mutations in the DNA methyltransferase 3B (DNMT3B) gene. A second human disorder (Rett syndrome) has been found to result from mutations in the MECP2 gene, which encodes a protein that binds to methylated DNA. Global genome demethylation caused by targeted mutations in the DNA methyltransferase-1 (Dnmt1) gene has shown that cytosine methylation plays essential roles in X-inactivation, genomic imprinting and genome stabilization. The majority of genomic 5-methylcytosine is now known to enforce the transcriptional silence of the enormous burden of transposons and retroviruses that have accumulated in the mammalian genome. It has also become clear that programmed changes in methylation patterns are less important in the regulation of mammalian development than was previously believed. Although a number of outstanding questions have yet to be answered (one of these questions involves the nature of the cues that designate sites for methylation at particular stages of gametogenesis and early development), studies of DNA methyltransferases are likely to provide further insights into the biological functions of genomic methylation patterns.

2,022 citations

Journal ArticleDOI
TL;DR: Developments of MR, including two-sample MR, bidirectional MR, network MR, two-step MR, factorial MR and multiphenotype MR, are outlined in this review.
Abstract: Observational epidemiological studies are prone to confounding, reverse causation and various biases and have generated findings that have proved to be unreliable indicators of the causal effects of modifiable exposures on disease outcomes. Mendelian randomization (MR) is a method that utilizes genetic variants that are robustly associated with such modifiable exposures to generate more reliable evidence regarding which interventions should produce health benefits. The approach is being widely applied, and various ways to strengthen inference given the known potential limitations of MR are now available. Developments of MR, including two-sample MR, bidirectional MR, network MR, two-step MR, factorial MR and multiphenotype MR, are outlined in this review. The integration of genetic information into population-based epidemiological studies presents translational opportunities, which capitalize on the investment in genomic discovery research.

1,686 citations

Journal ArticleDOI
TL;DR: A total of 20,000 parent-offspring transfers of alleles were examined through the genotyping within 40 CEPH reference families of 28 short tandem repeat polymorphisms (STRPs) located on chromosome 19, and the average mutation rate was nearly four times higher than the average rate for dinucleotide STRPs.
Abstract: A total of 20,000 parent-offspring transfers of alleles were examined through the genotyping within 40 CEPH reference families of 28 short tandem repeat polymorphisms (STRPs) located on chromosome 19. Forty-seven initial mutation events were detected in the STRPs using DNA from transformed lymphoblastoid cell lines, but less than half (39%) could be verified using DNA from untransformed cells. None of the cases where three alleles were observed in a single individual could be verified using DNA from untransformed cells. The average mutation rate for the chromosome 19 STRPs after correction for events which would not be detectable as Mendelian errors was 1.2 x 10(-3) per locus per gamete per generation. This rate may have been inflated by somatic as opposed to germline events. Observed mutation rates for individual STRPs ranged from 0 to 8 x 10(-3). The average mutation rate for tetranucleotide STRPs was nearly four times higher than the average rate for dinucleotide STRPs. For determination of the mode of mutation, events involving STRPs on other chromosomes were also examined. Of the events which were verified using DNA from untransformed lymphocytes or which were likely among those for which DNA from untransformed cells was not available: none were located at the sites of meiotic recombination, 91% involved the gain or loss of a single repeat unit, and 15 occurred in the male germline compared to 4 in the female germline (p = 0.01).

1,580 citations

Journal ArticleDOI
TL;DR: The general mechanisms of the circadian clockwork are reviewed, recent findings that elucidate tissue-specific expression patterns of the clock genes are described and the importance of circadian regulation in peripheral tissues for an organism's overall well-being is addressed.
Abstract: Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. This is achieved by ocular photoreception relaying signals to the suprachiasmatic nucleus (SCN) in the hypothalamus. Signals from the SCN cause the synchronization of independent circadian clocks throughout the body to appropriate phases. Signals that can entrain these peripheral clocks include humoral signals, metabolic factors, and body temperature. At the level of individual tissues, thousands of genes are brought to unique phases through the actions of a local transcription/translation-based feedback oscillator and systemic cues. In this molecular clock, the proteins CLOCK and BMAL1 cause the transcription of genes which ultimately feedback and inhibit CLOCK and BMAL1 transcriptional activity. Finally, there are also other molecular circadian oscillators which can act independently of the transcription-based clock in all species which have been tested.

1,550 citations

Performance
Metrics
No. of papers from the Journal in previous years
YearPapers
2023121
2022379
2021332
2020295
2019346
2018382