Formation of a Family of Long Intergenic Noncoding RNA Genes with an Embedded Translocation Breakpoint Motif in Human Chromosomal Low Copy Repeats of 22q11.2—Some Surprises and Questions

A family of long intergenic noncoding RNA (lincRNA) genes, FAM230 is formed via gene sequence duplication, specifically in human chromosomal low copy repeats (LCR) or segmental duplications. This is the first group of lincRNA genes known to be formed by segmental duplications and is consistent with current views of evolution and the creation of new genes via DNA low copy repeats. It appears to be an efficient way to form multiple lincRNA genes. But as these genes are in a critical chromosomal region with respect to the incidence of abnormal translocations and resulting genetic abnormalities, the 22q11.2 region, and also carry a translocation breakpoint motif, several intriguing questions arise concerning the presence and function of the translocation breakpoint sequence in RNA genes situated in LCR22s.

[1]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

[2]  T. Shaikh,et al.  A palindrome-mediated mechanism distinguishes translocations involving LCR-B of chromosome 22q11.2. , 2004, Human molecular genetics.

[3]  K. Morris,et al.  The rise of regulatory RNA , 2014, Nature Reviews Genetics.

[4]  S. B. Needleman,et al.  A general method applicable to the search for similarities in the amino acid sequence of two proteins. , 1970, Journal of molecular biology.

[5]  S. Magadum,et al.  Gene duplication as a major force in evolution , 2013, Journal of Genetics.

[6]  E. McConkey,et al.  Inversion, duplication, and changes in gene context are associated with human chromosome 18 evolution. , 2004, Genomics.

[7]  Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease , 2014 .

[8]  J. Lupski,et al.  Mendelian, non-Mendelian, multigenic inheritance, and epigenetics , 2020, Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease.

[9]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[10]  Igor Ulitsky,et al.  Evolution to the rescue: using comparative genomics to understand long non-coding RNAs , 2016, Nature Reviews Genetics.

[11]  Complexity of a small non-protein coding sequence in chromosomal region 22q11.2: presence of specialized DNA secondary structures and RNA exon/intron motifs , 2015, BMC Genomics.

[12]  T. Shaikh,et al.  Palindromic AT‐rich repeat in the NF1 gene is hypervariable in humans and evolutionarily conserved in primates , 2005, Human mutation.

[13]  G. Calin,et al.  The role of a new class of long noncoding RNAs transcribed from ultraconserved regions in cancer. , 2017, Biochimica et biophysica acta. Reviews on cancer.

[14]  K. Sullivan,et al.  Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes , 2007, The Lancet.

[15]  B. Morrow,et al.  Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. , 1999, American journal of human genetics.

[16]  T. Shaikh,et al.  Evolutionarily conserved low copy repeats (LCRs) in 22q11 mediate deletions, duplications, translocations, and genomic instability: An update and literature review , 2001, Genetics in Medicine.

[17]  E. Eichler,et al.  Masquerading repeats: paralogous pitfalls of the human genome. , 1998, Genome research.

[18]  P. Stankiewicz,et al.  AT-rich repeats associated with chromosome 22q11.2 rearrangement disorders shape human genome architecture on Yq12. , 2007, Genome research.

[19]  H. Kurahashi,et al.  Palindrome-Mediated Translocations in Humans: A New Mechanistic Model for Gross Chromosomal Rearrangements , 2016, Front. Genet..

[20]  Farooq Rashid,et al.  Primate-specific Long Non-coding RNAs and MicroRNAs , 2017, Genom. Proteom. Bioinform..

[21]  R. Stephens,et al.  Long homopurine•homopyrimidine sequences are characteristic of genes expressed in brain and the pseudoautosomal region , 2006, Nucleic acids research.

[22]  D. Zheng,et al.  Characterization of the past and current duplication activities in the human 22q11.2 region , 2011, BMC Genomics.

[23]  N. Delihas.  A family of long intergenic non-coding RNA genes in human chromosomal region 22q11.2 carry a DNA translocation breakpoint/AT-rich sequence , 2018, PloS one.

[24]  Astrid Gall,et al.  Ensembl 2018 , 2017, Nucleic Acids Res..

[25]  B. Emanuel,et al.  Chromosomal Translocations Mediated by Palindromic DNA , 2006, Cell cycle.

[26]  B. Morrow,et al.  AT-rich palindromes mediate the constitutional t(11;22) translocation. , 2001, American journal of human genetics.

[27]  J. Nielsen,et al.  Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics* , 2013, Molecular & Cellular Proteomics.

[28]  Ling-Ling Chen,et al.  The Diversity of Long Noncoding RNAs and Their Generation. , 2017, Trends in genetics : TIG.

[29]  B. Emanuel,et al.  Polymorphisms of the 22q11.2 breakpoint region influence the frequency of de novo constitutional t(11;22)s in sperm. , 2010, Human molecular genetics.

[30]  E. Eichler,et al.  Segmental duplications and the evolution of the primate genome , 2002, Nature Reviews Genetics.

[31]  Evan E Eichler,et al.  Human adaptation and evolution by segmental duplication. , 2016, Current opinion in genetics & development.

[32]  B. Emanuel,et al.  Chromosomal translocations and palindromic AT-rich repeats. , 2012, Current opinion in genetics & development.

[33]  P. Stankiewicz,et al.  Serial segmental duplications during primate evolution result in complex human genome architecture. , 2004, Genome research.

[34]  B. Emanuel,et al.  Molecular cloning of a translocation breakpoint hotspot in 22q11. , 2007, Genome research.

[35]  D. Zheng,et al.  Characterization of Human Pseudogene-Derived Non-Coding RNAs for Functional Potential , 2014, PloS one.

[36]  P. Stankiewicz,et al.  Molecular-evolutionary mechanisms for genomic disorders. , 2002, Current opinion in genetics & development.

[37]  J. Rinn,et al.  Linking RNA biology to lncRNAs , 2015, Genome research.

[38]  C. Feschotte,et al.  Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications. , 2014, Trends in genetics : TIG.

[39]  Peter J. Scambler,et al.  22q11.2 deletion syndrome. , 2015, Nature reviews. Disease primers.

[40]  S. Dhanasekaran,et al.  The landscape of long noncoding RNAs in the human transcriptome , 2015, Nature Genetics.

[41]  J. Espinosa.  On the Origin of lncRNAs: Missing Link Found. , 2017, Trends in genetics : TIG.

[42]  M. Frommer,et al.  Human satellite I sequences include a male specific 2.47 kb tandemly repeated unit containing one Alu family member per repeat. , 1984, Nucleic acids research.

[43]  B. Roe,et al.  Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. , 2000, Human molecular genetics.

[44]  Z. Tsai,et al.  Comparative genomic analyses highlight the contribution of pseudogenized protein-coding genes to human lincRNAs , 2017, BMC Genomics.