About classical molecular genetics, cytogenetic and molecular cytogenetic data not considered by Genome Reference Consortium and thus not included in genome browsers like UCSC, Ensembl or NCBI

Thomas Liehr

doi:10.1186/s13039-021-00540-7

Abstract

BackgroundThe Genome Reference Consortium (GRC) has according to its own statement the “mission to improve the human reference genome assembly, correcting errors and adding sequence to ensure it provides the best representation of the human genome to meet basic and clinical research needs”. Data from GRC is included in genome browsers like UCSC (University of California, Santa Cruz), Ensembl or NCBI (National Center for Biotechnology Information) and are thereby bases for scientific and diagnostically working human genetic community.MethodHere long standing knowledge deriving from classical molecular genetic, cytogenetic and molecular cytogenetic data, not being considered yet by GRC was revisited.ResultsThere were three major points identified: (1) GRC missed to including three chromosomal subbands, each, for 1q32.1, 2p21, 5q13.2, 6p22.3 and 6q21, which were defined by International System for Human Cytogenetic Nomenclature (ISCN) already back in 1980s; instead GRC included additional 6 subbands not ever recognized by ISCN. (2) GRC defined 34 chromosomal subbands of 0.1 to 0.9 Mb in size, while it is general agreement of cytogeneticists that it unlikely to detect chromosomal aberrations below 1–2 Mb in size by GTG-banding. And (3): still all sequences used in molecular cytogenetic routine diagnostics to detect heterochromatic and/ or pericentromeric satellite DNA sequences within the human genome are not included yet into human reference genome. For those sequences, localization and approximate sizes have been determined in the 1970s to 1990, and if included at least ~ 100 Mb of the human genome sequence could be added to the genome browsers.ConclusionOverall, taking into account the here mentioned points and correcting and including the data will definitely provide to the still not being completely finished mapping of the human genome.

Highlights

The Genome Reference Consortium (GRC) has according to its own statement the “mission to improve the human reference genome assembly, correcting errors and adding sequence to ensure it provides the best representation of the human genome to meet basic and clinical research needs”
In this paper it is discussed the following: in as much could GRC profit in its mission to “improve the human reference genome assembly, correcting errors and adding sequence to ensure it provides the best representation of the human genome to meet basic and clinical research needs” [8] by performing such an integrative view on the available data of the human genome as Joan-Ramon Daban did? This question is of immense practical meaning, as GRC-data is bases for genomic browsers like UCSC (University of California, Santa Cruz) [9], Ensembl [10] or NCBI (National Center for Biotechnology Information) [11], and those are being applied as backbone for correct interpretation of cytogenetic and molecular genetic diagnostic results
Individual band extensions in the chromosomal idiograms depicted in the genome browsers are not allowed to be changed based on results of sequencing. The latter has obviously been done when updating the browsers with new versions (Fig. 3). It could not be found out how GRC aligns sequencing data to G-bands by trypsin using Giemsa (GTG)-bands—the described changes of chromosomal band sizes suggest that it has been done possibly the following way: In the first version several years ago it was defined according to the knowledge from that time that e.g. band A on a certain chromosome is located between DNA-markers X and Z

Summary

Results

There were three major points identified: (1) GRC missed to including three chromosomal subbands, each, for 1q32.1, 2p21, 5q13.2, 6p22.3 and 6q21, which were defined by International System for Human Cytogenetic Nomenclature (ISCN) already back in 1980s; instead GRC included additional 6 subbands not ever recognized by ISCN. (2) GRC defined 34 chromosomal subbands of 0.1 to 0.9 Mb in size, while it is general agreement of cytogeneticists that it unlikely to detect chromosomal aberrations below 1–2 Mb in size by GTG-banding. (2) GRC defined 34 chromosomal subbands of 0.1 to 0.9 Mb in size, while it is general agreement of cytogeneticists that it unlikely to detect chromosomal aberrations below 1–2 Mb in size by GTG-banding. (3): still all sequences used in molecular cytogenetic routine diagnostics to detect heterochromatic and/ or pericentromeric satellite DNA sequences within the human genome are not included yet into human reference genome. For those sequences, localization and approximate sizes have been determined in the 1970s to 1990, and if included at least ~ 100 Mb of the human genome sequence could be added to the genome browsers

Conclusion

Background