Сytogenetic techniques in current biomedical research. part i: history and theoretical basis of human cytogenetics

Cytogenetics is an essential part of human genetics which studies the structure of chromosomes and their collection which is called karyotype. Cytogenetic techniques are employed while interrogating DNA organisation and compaction. Analysis of the chromosomal structure contributes to uncovering the molecular basis of various cellular processes in normal and pathological conditions. Furthermore, spectrum and frequency of chromosome abnormalities serves as an indicator of mutagenic effects. Cytogenetic techniques became indispensable for discovering the genetic causes of human diseases at different stages of ontogenesis. Genetic abnormalities are a common cause of impaired reproductive function, abnormal pregnancy, and neonatal malformations. Genetic screening for chromosomal abnormalities and congenital anomalies is a powerful tool for reducing the genetic load in human populations as well as disease, psychological and social burden on families and societies. This paper begins the cycle of lectures on molecular basis of human cytogenetics, cytogenetic techniques, and the corresponding research and clinical applications. The lecture is primarily aimed at biomedical students and physicians who often have an unmet need to analyse and interpret the results of cytogenetic analyses.

Placing women in Cytogenetics: Lore Zech and the chromosome banding technique

Background Scholars agree that Torbjörn Caspersson’s lab at the Institute of Medical Cell Research and Genetics at the Karolinska Institute, Sweden, played a key role in the first description of the so-called Q-banding technique. It laid the foundation for a new era of cytogenetic diagnostics and had a lasting impact in several areas of biology and medicine. Methods Based on a mixed-method approach, essential aspects of the history of human cytogenetics are considered via primary and secondary analysis of biographical interviews as well as the qualitative evaluation of bibliometrics. Drawing on interviews with colleagues of lab member Lore Zech (1923–2013) and contemporary publications, this paper illuminates the role of and contribution by Zech: To what extent is the discovery attached to her and what does her legacy look like today? Results The analysis of the contemporary witness interviews with colleagues, students and junior researchers shows that Lore Zech was a committed member of Caspersson's research group. In addition, memoirs by contemporary colleagues describe her outstanding skills in microscopy. The different sources paint a multifaceted picture. In addition to the historians' patterns of interpretation, different legacies can also be found within the peer group. Conclusions We argue that Zech represent the type of scientist who, although her research was acknowledged with several prizes, so far has not been part of the canon of pioneers of international cytogenetics.

Interstitial Deletion of 2q22.2q22.3 Involving the Entire ZEB2 Gene in a Case of Mowat-Wilson Syndrome

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by dysmorphic features, mental retardation, and congenital heart disease (CHD). MWS results from microdeletions of chromosome 2q23 or de novo SNVs involving the ZEB2 gene. Here, we report on an Egyptian MWS patient diagnosed by chromosomal microarray (CMA). A 1-year-old male child was referred to the CHD clinic, National Research Centre, presenting with dysmorphic features and CHD. The patient was referred to the human cytogenetics department for cytogenetic analysis and for screening of subtelomere rearrangements and microdeletion loci, using MLPA, and all revealed normal results. CMA revealed an interstitial 2.27-Mb microdeletion in chromosome 2q, involving the entire ZEB2 gene and other genes. This study emphasizes the significance of CMA in the detection of microdeletions/microduplications and as a screening tool in cases presenting with CHD and extracardiac manifestations. MWS should be suspected in patients presenting with the characteristic facial dysmorphism, developmental delay, seizures, Hirschsprung disease, and congenital heart anomalies, especially those involving the pulmonary arteries or pulmonary valves. It is recommended to include the ZEB2 locus in the MLPA microdeletions probes.

The history of emergence and development of medical genetics in Russia

The early years of human genetics in Russia were distinguished by a pronounced interest in eugenics, pioneering methodological achievements in human cytogenetics, systematic studies of the contribution of heredity to the development of multifactorial diseases, the physical and mental human characteristics. The vast scientific infrastructure in genetics that had developed by the mid-1930s was demolished in a series of political decisions beginning with the campaigns to eradicate eugenic ideas and ending with the notorious 1948 VASKhNIL session, which entailed a complete ban on the genetics. For almost 25 years, key to the development of this science throughout the world, its progress in Russia was first completely frozen, and then retarded profoundly. The revival of medical genetics went in different ways, by virtue of many prominent specialists in various fields of human genetics, formed before the era of repression. New scientific schools were founded by them and their disciples. Despite the enormous gap in the level of domestic and world genetics, which lagged even after the ban was lifted, a series of important works in the field of radiation mutagenesis, population genetics, cytogenetics, as well as a number of world class achievements in the field of biochemical genetics and the study of metabolic diseases, should be noted. Gradually, as the state recognized the importance of genetics for medicine, an extensive medical genetic service arose in the countrys healthcare system. The conditional point of the final rehabilitation of medical genetics can be recognized in the emergence of departments of this discipline in medical schools throughout the country in the late 1980s. Despite the gap, still persisting between the worlds level of medical genetic science and the current state of it in our country, this gap has significantly reduced nowadays.

Standard Making in Cytogenetics: the Manufacture, Circulation and Reproduction of Chromosome Images

The first reliable pattern of the human chromosome set was manufactured between the late 1950s and early 1960s. This paper will account for the historical background of such reliability, of the production of a reference, an image, the schematic figure – the ideogram – that represented what would from then on be held in the minds of medical practitioners and laboratory scientists of human cytogenetics as the cytological identity of being human. Human genetics as a history of images and the skills of drawing, making photo(micro) graphs and diagrams, developed through a reference drawn on the basis of the consensus reached by a small group of early human cytogeneticists in Denver in 1960. Schemes and idealizations, as well as the fully realistic transposition of the contours and interiors of each chromosome, participated in the emergence of a particular, specific and enduring way of representing the tiny parts of the cell where division began, and accounting for both the forms and function of chromosomes at the origins of medical genetics.

Women in Early Human Cytogenetics: An Essay on a Gendered History of Chromosome Imaging

Alongside the renowned male pioneers of medical cytogenetics, many women participated in investigations at the laboratory bench and the bedside, both in Europe and the Americas. These women were committed to this new biological and clinical practice—cytogenetics, the origins of contemporary genetic diagnosis—and contributed to the creation of new biological concepts and settings centered on the study of chromosome imaging. This paper will review the contributions made by a group of woman scientists from a wide geographical distribution, situating their names and research agendas within the history of a field dating back to early plant and insect cytogenetics. Rather than an exhaustive compendium of women geneticists, this essay presents a kind of historical reconstruction that can be achieved by placing women at center stage in their geographies and networks of circulating cytogenetic knowledge and practices thereby relating a history of genetic images though the work carried out by women, retrieving their agency and constructing an inclusive history of an influential contemporary biomedical practice as it gained increasing influence in the laboratory and the clinic.

From Human Cytogenetics to Human Chromosomics

Background: The concept of “chromosomics” was introduced by Prof. Uwe Claussen in 2005. Herein, the growing insights into human chromosome structure finally lead to a “chromosomic view” of the three-dimensional constitution and plasticity of genes in interphase nuclei are discussed. This review is dedicated to the memory of Prof. Uwe Claussen (30 April 1945–20 July 2008). Recent findings: Chromosomics is the study of chromosomes, their three-dimensional positioning in the interphase nucleus, the consequences from plasticity of chromosomal subregions and gene interactions, the influence of chromatin-modification-mediated events on cells, and even individuals, evolution, and disease. Progress achieved in recent years is summarized, including the detection of chromosome-chromosome-interactions which, if damaged, lead to malfunction and disease. However, chromosomics in the Human Genetics field is not progressing presently, as research interest has shifted from single cell to high throughput, genomic approaches. Conclusion: Chromosomics and its impact were predicted correctly in 2005 by Prof. Claussen. Although some progress was achieved, present reconsiderations of the role of the chromosome and the single cell in Human Genetic research are urgently necessary.

Circulating biomedical images: Bodies and chromosomes in the post-eugenic era

This essay presents the early days of human cytogenetics, from the late 1950s until the mid 1970s, as a historical series of images. I propose a chronology moving from photographs of bodies to chromosome sets, to be joined by ultrasound images, which provided a return to bodies, by then focused on the unborn. Images carried ontological significance and, as I will argue, are principal characters in the history of human cytogenetics. Inspired by the historiography of heredity and genetics, studies on visual cultures, the conceptualization of circulation, and the sociology of pregnancy, I suggest that cytogenetics, through its focus on pregnancy, pregnant women, and their offspring, found strategic living materials that stabilized human chromosome studies as a biomedical, post-eugenics practice. The historicity of each path displays a wide circulation of objects, tools, and methods that condensed on images that shared in the centuries-old visual expertise that medicine and botany had manufactured.