PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 3326942

Genetic linkage: sampling issues and multipoint mapping.

M A Spence
View original source ↗Export metadata ↓

Abstract

Genetic linkage is an important tool in determining the genetic contribution to the etiology of behavior disorders and psychiatric disease. Successful linkage studies employ large sample sizes. It is of particular relevance in psychiatric diseases, where the clinical workup is so extensive, to evaluate sample requirements critically. Recent studies indicate that extensive sampling, out to second-degree relatives, will not assist in identifying linkages although it may inflate the sample size considerably. The impact of the assumption about the mode of inheritance of the psychiatric trait and the effect of reduced penetrance are discussed. Multipoint mapping has the added advantage of using information from many markers simultaneously. This is helpful both in identifying individuals at risk to develop disease and in locating a gene with sufficient precision to determine the gene product. There are complications in applying multipoint mapping but these are generally of a technical nature and soluble. Recent suggestions for handling complications for multipoint mapping are evaluated. The correct design of the sampling procedure for selecting families and for selecting marker loci to use will greatly reduce the volume of work required for linkage studies and enhance the chances for success.

Explore related subjects

Chromosome AberrationsChromosome DisordersChromosome MappingGenetic LinkageGenetic MarkersHumansMental DisordersJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M A Spence. 1987. Genetic linkage: sampling issues and multipoint mapping.. https://doi.org/10.1016/0022-3956(87)90114-2

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1992

Karyotypic derivation of H9 cell line expressing human immunodeficiency virus susceptibility.

BACKGROUND: The T-cell lymphoma HUT78 cell line and the H9 clone of the CD4-positive HT cell line, derived from HUT78, are known to be genetically identical on the basis of allozyme (allelic isozyme) patterns and DNA fingerprinting, but the chromosome compositions of these cell lines have not been determined. The HT cell line and its H9 clone carry susceptibility to the human immunodeficiency virus (HIV). PURPOSE: The purpose of this study was to examine specific chromosome changes linking the expression of the HIV susceptibility that is unique to H9 cells by characterizing the karyotypes of the HUT78 and the H9 cell lines, by comparing chromosome differences between these lines, and by evaluating the relationships between them. METHODS: Air-dried chromosome slides were prepared, and the fast Giemsa-trypsin method was used to delineate G-bands. The numerical distribution of chromosomes from the two cell lines was determined, and complete chromosome analysis in 47 HUT78 metaphases and 21 H9 metaphases with discernible G-banding was used to specify the modal karyotypes of each cell line. RESULTS: Both cell lines had complex karyotypes that contained 47%-65% structurally modified marker chromosomes. The distribution of numbers of chromosomes in HUT78 cultures was broad. There were two distinct modal numbers of chromosomes at 42 and 43 and at 73, resulting from the presence of three actively growing sublines: two hypodiploid (1s) sublines (HUT78/1sA and HUT78/1sB) and a hypertriploid (2s) subline (HUT78/2s), respectively. HUT78/1sA and HUT78/1sB differed by five reciprocal chromosome replacements, and HUT78/2s had double copies of most of the chromosomes in 1s cells. H9 and HUT78/2s had had 21 matching markers, 10 of which were paired; contained 21 chromosomes with the same number of copies; consistently lacked eight homologous normal chromosomes; and showed close modal numbers of chromosomes at 69 and 73, respectively. CONCLUSIONS: Derivation of the 2s subline from the 1s subline by polyploidization is apparent. All lines apparently had the same progenitor cell population, and HUT78/2s represents an intermediate linking HUT78/1s to H9. IMPLICATIONS: These data should be useful for studying specific chromosome changes linking the expression of the HIV susceptibility unique to H9 cells. Karyologic studies such as those presented here can provide data (a) to clearly identify the clonal cell population of a subline, (b) to examine relationships among sublines of the same progenitor, and (c) to provide a clue that may link a subtle chromosome change to a phenotypic expression.

Chromosome Aberrations↗
PubMed1992

Cloning of cDNAs of the MLL gene that detect DNA rearrangements and altered RNA transcripts in human leukemic cells with 11q23 translocations.

Recurring chromosomal abnormalities involving translocations at chromosome 11 band q23 are associated with human myeloid and lymphoid leukemia as well as lymphoma. We have identified the gene located at this break-point and have named it MLL (for myeloid-lymphoid, or mixed-lineage, leukemia). The t(4;11), t(6;11), t(9;11), and t(11;19) are among the most common reciprocal translocations in leukemia cells involving this chromosomal band. We now have evidence that the breakpoints in all of these translocations are clustered within a 9-kilobase (kb) BamHI genomic region of the MLL gene. By Southern blot hybridization using a 0.7-kb BamHI cDNA fragment of the MLL gene called MLL 0.7B, we have detected rearrangements of DNA from cell lines and patient material with an 11q23 translocation in this region. Northern blot analyses indicate that this gene has multiple transcripts, some of which appear to be lineage-specific. In normal pre-B cells, four transcripts of 12.5, 12.0, 11.5, and 2.0 kb are detected. These transcripts are also present in monocytoid cell lines with additional hybridization to a 5.0-kb transcript, indicating that expression of different-sized MLL transcripts may be associated with normal hematopoietic lineage development. In a cell line with a t(4;11), the expression of the 12.5-, 12.0-, and 11.5-kb transcripts is reduced, and there is evidence of three other altered transcripts of 11.5, 11.25, and 11.0 kb. Thus, these 11q23 translocations result in rearrangements of the MLL gene and may lead to altered function(s) of MLL and of other gene(s) involved in the translocation.

Chromosome Aberrations↗