The manipulation of chromosomes by mankind: the uses of microcell-mediated chromosome transfer

Abstract

Microcell-mediated chromosome transfer (MMCT) was a technique originally developed in the 1970s to transfer exogenous chromosome material into host cells. Although, the methodology has not changed considerably since this time it is being used to great success in progressing several different fields in modern day biology. MMCT is being employed by groups all over the world to hunt for tumour suppressor genes associated with specific cancers, DNA repair genes, senescence-inducing genes and telomerase suppression genes. Some of these genomic discoveries are being investigated as potential treatments for cancer. Other fields have taken advantage of MMCT, and these include assessing genomic stability, genomic imprinting, chromatin modification and structure and spatial genome organisation. MMCT has also been a very useful method in construction and manipulation of artificial chromosomes for potential gene therapies. Indeed, MMCT is used to transfer mainly fragmented mini-chromosome between cell types and into embryonic stem cells for the construction of transgenic animals. This review briefly discusses these various uses and some of the consequences and advancements made by different fields utilising MMCT technology.

Identification of PITX1 as a TERT Suppressor Gene Located on Human Chromosome 5

“…Microcell-mediated chromosome transfer (MMCT) is a powerful tool for (i) gene hunting, (ii) the elucidation of the essential function of products that are expressed from a specific chromosome with its endogenous physical system, and (iii) understanding the role of the components of chromosomes and understanding genome organization (12,31). In addition, the functional analysis of cells that have undergone MMCT using a human chromosome truncated at specific sites enables the precise mapping and identification of genes involved in a particular cell function, such as telomerase regulation, during cellular aging and metastasis.…”

“…In addition, the functional analysis of cells that have undergone MMCT using a human chromosome truncated at specific sites enables the precise mapping and identification of genes involved in a particular cell function, such as telomerase regulation, during cellular aging and metastasis. This method also can be used to identify DNA repair genes whose mutation/deletion is responsible for various inherited genetic defects, to generate transgenic mice with introduced human chromosomes, and to establish animal models of human diseases (12,31). Advances have been made in the technology of chromosome engineering using DNA targeting through homologous recombination.…”

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models

“…Chromosome mapping is based on a complementation study [11,12], and involves the introduction of a human chromosome via MMCT to rescue the phenotype of the model cells, such as cancer cell lines or disease model cells. This technique has been used for the identification of genes related to tumor suppression [13,14], genomic imprinting [15,16], DNA repair [17][18][19], metastasis and genomic instability [20], telomerase regulation [21][22][23], mitochondrial disorders [24], and lysosomal storage diseases [25].…”

Nuclear organisation in totipotent human nuclei and its relationship to chromosomal abnormality

“…However, we are aware of no reported evidence of significantly altered chromosome territory position associated with aneuploidy, despite the alteration in gene expression that most ensue in an aneuploid cell (Croft et al, 1999). This is also true for artificially created trisomies (Upender et al, 2004;Sengupta et al, 2006) and polyploidies (Kost-Alimova et al, 2004) generated by micro-cell-mediated chromosome transfer, in which altered gene expression (trisomies) and induced chromosome instability (polyploidies) are seen (Meaburn et al, 2005b).…”