Finishing the finished human chromosome 22 sequence

Cole, Charlotte G.; McCann, Owen T.; Collins, John; Oliver, Karen; Willey, David L.; Gribble, Susan; Yang, Fengtang; McLaren, Karen; Rogers, Jane; Ning, Zemin; Beare, David; Dunham, Ian

doi:10.1186/gb-2008-9-5-r78

Cited by 22 publications

(19 citation statements)

References 38 publications

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“…Together with the 2.85 Gb finished sequence, this gives an estimated human genome size 3.1 Gb. However, the efforts to close the gaps continue (65,66) and the exact human genome size will not be known until this work is completed. At the same time, one has to be aware of the variation in the human genome, which may result in differences in genome size between individuals (67).…”

Section: Using a Sequenced Reference Standardmentioning

confidence: 99%

Nuclear genome size: Are we getting closer?

2010

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Correct information on genome size is important in many areas of research. For a long time, scientists have been struggling to understand the reason for the huge variation in eukaryotic genome size and its biological significance. More recently, the knowledge on genome size has become important to structure genome sequencing projects as their scale and cost depend on genome size. Despite the fact that the first estimates of genome size in eukaryotes were made more than 50 years ago, we are still not quite sure about the exact genome size in practically all animal and plant species. Moreover, different estimates continue to be published for the same species. These discrepancies compromise data comparison and interpretation and point to methodological problems, which include standardization. This article assesses the current state of DNA reference standards for flow cytometry and the issues related to their calibration. ' 2010 International Society for Advancement of CytometryKey terms cytometric techniques; reference standards; genome sequencing; conversion factor; nuclear DNA content; C-value MOST of the genetic information in eukaryotes is localized in the cell nucleus and numerous attempts have been made to determine the quantity of nuclear DNA, especially after various lines of evidence associated DNA with genes (1). It soon became clear that the amount of DNA per nucleus is relatively constant in somatic cells of a given species and that sperm cells have approximately half the DNA amount found for somatic cells (2,3). These experiments provided independent data to support the hereditary role of DNA and marked the beginning of numerous fruitful lines of research and applications, many of them still important today, all relying on the ability to determine DNA amounts in cell nuclei.The early determinations were made colorimetrically on DNA extracted from a known number of cells although the presence of cells in different cell cycle phases could compromise the accuracy of these estimates. The colorimetric approach made identification of subpopulations of cells with different DNA amounts impossible. However, cytometric methods suitable for measurement of absorbance of light in individual nuclei (either using UV light with non-stained nuclei and/or monochromatic visible light with nuclei stained by the Feulgen reaction) were already available during the 1940s and were used to discover the presence of cells with different classes of DNA amounts. Such cells were observed in a variety of animal tissues and were associated with polyploidy and polyteny (4,5). The presence of nuclei with 2, 4, 8, 16, or 32 times the haploid value was described in plant tissues by Swift (6) who introduced the ''C'' terminology to classify nuclear DNA amounts. In this terminology, DNA classes are labeled as C, 2C, 4C, 8C, etc. to characterize DNA amounts of nuclei by multiples of the DNA amount in a complete chromosome set in a non-replicated haploid nucleus, which has the class C DNA amount.At the beginning of the 1950s, biochem...

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Section: Using a Sequenced Reference Standardmentioning

confidence: 99%

Nuclear genome size: Are we getting closer?

2010

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“…Human chromosome 22 spans about 50 million base pairs containing more than 800 annotated genes (NCBI Build 37.1 of the human genome) [Dunham et al, 1999;Cole et al, 2008]. The proximal region of this chromosome is significantly enriched in low copy repeats (LCRs), including LCR22A to LCR22H ( fig.…”

Section: Identification Of Copy Numbermentioning

confidence: 99%

Identification of Copy Number Variants on Human Chromosome 22 in Patients with a Variety of Clinical Findings

Graf

Ramalingam

et al. 2011

Cytogenet Genome Res

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The aims of this study were to create a copy number variant (CNV) profile of human chromosome 22 and to establish a genotype-phenotype correlation for patients with genomic abnormalities on chromosome 22. Thus, 1,654 consecutive pediatric patients with a diversity of clinical findings were evaluated by high-resolution chromosomal microarray analysis (CMA). We identified 25 individuals with abnormal CNVs on chromosome 22, representing 1.5% of the cases analyzed in this cohort. Meanwhile, we detected 1,298 benign CNVs on this chromosome in these individuals. Twenty-one of the 25 abnormal CNVs and the majority of the benign CNVs occurred through involvement of the 8 unstable genomic regions enriched with low copy repeats (LCR22A–H). The highly dynamic status of LCR22s within the 22q11 region facilitates the formation of diverse genomic abnormalities. This CNV profile provides a general perspective of the spectrum of chromosome 22 genomic imbalances and subsequently improves the CNV-phenotype correlations.

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“…Further, although whole-genome short-read 5 sequencing is now routine, alignment of short sequencing reads to the human reference sequence generally fails to detect and assemble large structural variants and repetitive regions like the LCR22s. Due to the length of the duplications, even assemblies using longer-range technologies like PacBio and 10X Genomics linked reads have been unable to assemble these regions (31,32). To resolve these problems, we have generated a de novo assembly of ?…”

Section: Discussionmentioning

confidence: 99%

“…The latter is HPRT-deficient, allowing selection of fused cell colonies. Briefly, human EBV cells were fused with host cells in the presence of PEG and grown under selective HAT medium 31 . Cell colonies were screened by PCR and interphase FISH to select only those containing a del (22)(q11.21).…”

Section: Construction and Screening Of Hybrid Cell Linesmentioning

confidence: 99%

The 22q11 low copy repeats are characterized by unprecedented size and structure variability

Demaerel¹,

Mostovoy

Yilmaz

et al. 2018

Preprint

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Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving genome 25 variability and evolution. The chromosome 22 LCRs (LCR22s) are amongst the most complex regions in the genome and their structure remains unresolved. These LCR22s mediate non-allelic homologous recombination (NAHR) leading to the 22q11 deletion syndrome (22q11DS), causing the most frequent genomic disorder. Using fiber FISH optical mapping, we have de novo assembled the LCR22s in 33 cell lines. We observed a high level of variation in LCR22 structures, including 26 different haplotypes of LCR22A with alleles ranging from 250 Kb to over 2,000 Kb. 30An additional four haplotypes were detected using Bionano mapping. Further, Bionano maps generated from 154 individuals from different populations suggested significantly different LCR22 haplotype frequencies between populations. Furthermore, haplotype analysis in nine 22q11DS patients resulted in the localization of the NAHR site to a 160 Kb paralog between LCR22A and -D in seven patients and to a 31 Kb region in two individuals with a rearrangement between LCR22A and -B.. This 31 Kb region contains a palindromic AT-rich repeat known to be a 35 driver of chromosomal rearrangements. Our study highlights an unprecedented level of polymorphism in the structure of LCR22s, which are likely still evolving. We present the most comprehensive map of LCR22 variation to date, paving the way towards investigating the role of LCR variation as a driver of 22q11 rearrangements and the phenotypic variability in 22q11DS patients as well as in the general population. 40 45

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Finishing the finished human chromosome 22 sequence

Cited by 22 publications

References 38 publications

Nuclear genome size: Are we getting closer?

Nuclear genome size: Are we getting closer?

Identification of Copy Number Variants on Human Chromosome 22 in Patients with a Variety of Clinical Findings

The 22q11 low copy repeats are characterized by unprecedented size and structure variability

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