The complete plastomes of red fleshed pitaya (Selenicereus monacanthus) and three related Selenicereus species: insights into gene losses, inverted repeat expansions and phylogenomic implications

Huntington disease (HD) is caused by a pathologic cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. Typical adult-onset disease occurs with a minimum of 40 repeats. With more than 60 CAG repeats, patients can have juvenile-onset disease (jHD), with symptom onset by the age of 20 years. We report a case of a boy with extreme early onset, paternally inherited jHD, with symptom onset between 18 and 24 months. He was found to have 250 to 350 CAG repeats, one of the largest repeat expansions published to date. At initial presentation, he had an ataxic gait, truncal titubation, and speech delay. Magnetic resonance imaging showed cerebellar atrophy. Over time, he continued to regress and became nonverbal, wheelchair-bound, gastrostomy-tube dependent, and increasingly rigid. His young age at presentation and the ethical concerns regarding HD testing in minors delayed his diagnosis.

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Formation of Large Palindromic DNA by Homologous Recombination of Short Inverted Repeat Sequences in Saccharomyces cerevisiae

Genetics ◽

10.1093/genetics/161.3.1065 ◽

2002 ◽

Vol 161 (3) ◽

pp. 1065-1075

Author(s):

David K Butler ◽

David Gillespie ◽

Brandi Steele

Keyword(s):

Homologous Recombination ◽

Inverted Repeat ◽

Excision Repair ◽

Strand Break ◽

Double Strand Break ◽

Repeat Sequence ◽

Inverted Repeat Sequence ◽

Repeat Sequences ◽

Dna Double Strand Break ◽

Intermolecular Reaction

Abstract Large DNA palindromes form sporadically in many eukaryotic and prokaryotic genomes and are often associated with amplified genes. The presence of a short inverted repeat sequence near a DNA double-strand break has been implicated in the formation of large palindromes in a variety of organisms. Previously we have established that in Saccharomyces cerevisae a linear DNA palindrome is efficiently formed from a single-copy circular plasmid when a DNA double-strand break is introduced next to a short inverted repeat sequence. In this study we address whether the linear palindromes form by an intermolecular reaction (that is, a reaction between two identical fragments in a head-to-head arrangement) or by an unusual intramolecular reaction, as it apparently does in other examples of palindrome formation. Our evidence supports a model in which palindromes are primarily formed by an intermolecular reaction involving homologous recombination of short inverted repeat sequences. We have also extended our investigation into the requirement for DNA double-strand break repair genes in palindrome formation. We have found that a deletion of the RAD52 gene significantly reduces palindrome formation by intermolecular recombination and that deletions of two other genes in the RAD52-epistasis group (RAD51 and MRE11) have little or no effect on palindrome formation. In addition, palindrome formation is dramatically reduced by a deletion of the nucleotide excision repair gene RAD1.

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Generation of an induced pluripotent stem cell line (ZZUi020-A) from a patient with Parkinson’s disease harboring the intermediate-length GGC repeat expansions in the NOTCH2NLC gene

Stem Cell Research ◽

10.1016/j.scr.2021.102257 ◽

2021 ◽

Vol 52 ◽

pp. 102257

Author(s):

Yu Fan ◽

Fen Liu ◽

Li-yuan Fan ◽

Cheng-yuan Mao ◽

Han Liu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Stem Cell ◽

Cell Line ◽

Pluripotent Stem Cell ◽

Induced Pluripotent Stem Cell ◽

Stem Cell Line ◽

Repeat Expansions ◽

Induced Pluripotent

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The chloroplast genome evolution of Venus slipper (Paphiopedilum): IR expansion, SSC contraction, and highly rearranged SSC regions

BMC Plant Biology ◽

10.1186/s12870-021-03053-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yan-Yan Guo ◽

Jia-Xing Yang ◽

Ming-Zhu Bai ◽

Guo-Qiang Zhang ◽

Zhong-Jian Liu

Keyword(s):

Gene Order ◽

Inverted Repeat ◽

Single Copy ◽

Gene Content ◽

Comparative Genomic ◽

Substitution Rates ◽

Plastome Evolution ◽

Chloroplast Genomes ◽

Ideal System ◽

Small Single Copy

Abstract Background Paphiopedilum is the largest genus of slipper orchids. Previous studies showed that the phylogenetic relationships of this genus are not well resolved, and sparse taxon sampling documented inverted repeat (IR) expansion and small single copy (SSC) contraction of the chloroplast genomes of Paphiopedilum. Results Here, we sequenced, assembled, and annotated 77 plastomes of Paphiopedilum species (size range of 152,130 – 164,092 bp). The phylogeny based on the plastome resolved the relationships of the genus except for the phylogenetic position of two unstable species. We used phylogenetic and comparative genomic approaches to elucidate the plastome evolution of Paphiopedilum. The plastomes of Paphiopedilum have a conserved genome structure and gene content except in the SSC region. The large single copy/inverted repeat (LSC/IR) boundaries are relatively stable, while the boundaries of the inverted repeat and small single copy region (IR/SSC) varied among species. Corresponding to the IR/SSC boundary shifts, the chloroplast genomes of the genus experienced IR expansion and SSC contraction. The IR region incorporated one to six genes of the SSC region. Unexpectedly, great variation in the size, gene order, and gene content of the SSC regions was found, especially in the subg. Parvisepalum. Furthermore, Paphiopedilum provides evidence for the ongoing degradation of the ndh genes in the photoautotrophic plants. The estimated substitution rates of the protein coding genes show accelerated rates of evolution in clpP, psbH, and psbZ. Genes transferred to the IR region due to the boundary shift also have higher substitution rates. Conclusions We found IR expansion and SSC contraction in the chloroplast genomes of Paphiopedilum with dense sampling, and the genus shows variation in the size, gene order, and gene content of the SSC region. This genus provides an ideal system to investigate the dynamics of plastome evolution.

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A 160-bp Palindrome Is a Rad50·Rad32-Dependent Mitotic Recombination Hotspot inSchizosaccharomyces pombe

Genetics ◽

10.1093/genetics/161.1.461 ◽

2002 ◽

Vol 161 (1) ◽

pp. 461-468 ◽

Cited By ~ 6

Author(s):

Joseph A Farah ◽

Edgar Hartsuiker ◽

Ken-ichi Mizuno ◽

Kunihiro Ohta ◽

Gerald R Smith

Keyword(s):

Secondary Structure ◽

Schizosaccharomyces Pombe ◽

Inverted Repeat ◽

Mitotic Recombination ◽

Genome Integrity ◽

Recombination Hotspot ◽

Nuclease Domain ◽

Palindromic Sequences

AbstractPalindromic sequences can form hairpin and cruciform structures that pose a threat to genome integrity. We found that a 160-bp palindrome (an inverted repeat of 80 bp) conferred a mitotic recombination hotspot relative to a control nonpalindromic sequence when inserted into the ade6 gene of Schizosaccharomyces pombe. The hotspot activity of the palindrome, but not the basal level of recombination, was abolished by a rad50 deletion, by a rad50S “separation of function” mutation, or by a rad32-D25A mutation in the nuclease domain of the Rad32 protein, an Mre11 homolog. We propose that upon extrusion of the palindrome the Rad50·Rad32 nuclease complex recognizes and cleaves the secondary structure thus formed and generates a recombinogenic break in the DNA.

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REscan: inferring repeat expansions and structural variation in paired-end short read sequencing data

Bioinformatics ◽

10.1093/bioinformatics/btaa753 ◽

2020 ◽

Author(s):

Russell Lewis McLaughlin

Keyword(s):

Structural Variation ◽

Sequence Data ◽

Neurological Diseases ◽

Repeat Expansion ◽

Sequencing Data ◽

Short Read ◽

Short Read Sequencing ◽

Repeat Expansions ◽

Paired End Sequencing

Abstract Motivation Repeat expansions are an important class of genetic variation in neurological diseases. However, the identification of novel repeat expansions using conventional sequencing methods is a challenge due to their typical lengths relative to short sequence reads and difficulty in producing accurate and unique alignments for repetitive sequence. However, this latter property can be harnessed in paired-end sequencing data to infer the possible locations of repeat expansions and other structural variation. Results This article presents REscan, a command-line utility that infers repeat expansion loci from paired-end short read sequencing data by reporting the proportion of reads orientated towards a locus that do not have an adequately mapped mate. A high REscan statistic relative to a population of data suggests a repeat expansion locus for experimental follow-up. This approach is validated using genome sequence data for 259 cases of amyotrophic lateral sclerosis, of which 24 are positive for a large repeat expansion in C9orf72, showing that REscan statistics readily discriminate repeat expansion carriers from non-carriers. Availabilityand implementation C source code at https://github.com/rlmcl/rescan (GNU General Public Licence v3).

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