Cited by 908Genome Rearrangement AlgorithmsGenomic variations and chromosomal abnormalitiesChromosomal and Genetic Variations

Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits

Lupski, James R·1998·Trends in Genetics

Abstract

Molecular medicine began with Pauling's seminal work, which recognized sickle-cell anemia as a molecular disease, and with Ingram's demonstration of a specific chemical difference between the hemoglobins of normal and sickled human red blood cells. During the four decades that followed, investigations have focused on the gene--how mutations specifically alter DNA and how these changes affect the structure and expression of encoded proteins. Recently, however, the advances of the human genome project and the completion of total genome sequences for yeast and many bacterial species, have enabled investigators to view genetic information in the context of the entire genome. As a result, we recognize that the mechanisms for some genetic diseases are best understood at a genomic level. The evolution of the mammalian genome has resulted in the duplication of genes, gene segments and repeat gene clusters. This genome architecture provides substrates for homologous recombination between nonsyntenic regions of chromosomes. Such events can result in DNA rearrangements that cause disease.

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Crossref · 10.1016/s0168-9525(98)01555-8

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  • The segmental-duplication-flanked de novo CNVs most likely arose by nonallelic homologous recombination.

    “This class of CNV most likely occurred by nonallelic homologous recombination (NAHR) (Lupski, 1998).”

    From High frequencies of de novo CNVs in bipolar disorder and schizophrenia (2011) · cites this paper as Lupski, 1998

  • Many CNV loci strongly implicated in human disease are hotspots for non-allelic homologous recombination, a process usually mediated by flanking segmental duplications.

    “Many CNV loci that have been strongly implicated in human disease are hotspots for non-allelic homologous recombination (NAHR), a process which in most cases is mediated by flanking segmental duplications 21.”

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Authors
Lupski, J. R.
Affiliations
Baylor College of Medicine (US)
Corresponding author
Lupski, James R
Venue
Trends in Genetics
Publisher
Elsevier BV
Published
1998-10
Volume
14
Issue
10
Pages
417-422
ISSN
0168-9525 (ISSN-L)
OpenAlex
W1997647094
Cited by
908
References
76
Citations by year
2026: 8 · 2025: 12 · 2024: 25 · 2023: 19 · 2022: 24 · 2021: 18 · 2020: 21 · 2019: 22 · 2018: 13 · 2017: 20 · 2016: 24 · 2015: 40 · 2014: 33 · 2013: 42 · 2012: 41
FWCI
4.72
Type
journal article
Language
en
Open access
closed
Locations
  • Trends in Genetics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Center for Research Resources (M01RR000188)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 24064, P30HD024064, HD94021)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
genomic disorders, DNA rearrangement, structural variants, homologous recombination, gene duplication, mammalian genome evolution, human disease, sickle cell disease, molecular medicine
MeSH terms
Chromosome Aberrations, Humans, Gene Rearrangement, Genetic Diseases, Inborn

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