III Antibodies A Monoclonal antibodies against determinants of the HLA-A,-B,-C glycoproteins and pjmicroglobulin 1. Antibodies against species specific, non-polymorphic determinants 2. Antibodies against polymorphic HLA-A,-B,-C determinants B Monoclonal antibodies against HLA-DRw determinants 1. Antibody against a species specific HLA-DRw determinants 2. Antibodies against polymorphic HLA-DRw determinants

Citation-classic - monoclonal-antibodies for analysis of the hla system

REVIEW ARTICLE Genomewide Scans of Complex Human Diseases: True Linkage Is Hard to Find

Many "complex" human diseases, which involve multiple genetic and environmental determinants, have increased in incidence during the past 2 decades. During the same time period, considerable effort and expense have been expended in whole-genome screens aimed at detection of genetic loci contributing to the susceptibility to complex human diseases. However, the success of positional cloning attempts based on whole-genome screens has been limited, and many of the fundamental questions relating to the genetic epidemiology of complex human disease remain unanswered. Both to review the success of the positional cloning paradigm as applied to complex human disease and to investigate the characteristics of the whole-genome scans undertaken to date, we created a database of 101 studies of complex human disease, which were found by a systematic Medline search (current as of December 2000). We compared these studies, concerning 31 different human complex diseases, with regard to design, methods, and results. The "significance" categorizations proposed by Lander and Kruglyak were used as criteria for the "success" of a study. Most (66.3% [n=67]) of the studies did not show "significant" linkage when the criteria of Lander and Kruglyak (1995) were used, and the results of studies of the same disease were often inconsistent. Our analyses suggest that no single study design consistently produces more-significant results. Multivariate analysis suggests that the only factors independently associated with increased study success are (a) an increase in the number of individuals studied and (b) study of a sample drawn from only one ethnic group. Positional cloning based on whole-genome screens in complex human disease has proved more difficult than originally had been envisioned; detection of linkage and positional cloning of specific disease-susceptibility loci remains elusive.

http://www.alliot.fr/BIO/PDF/AJHGv69p936.pdf

Genomewide Scans of Complex Human Diseases: True Linkage Is Hard to Find

This review summarizes reports of recurrent DNA sequence copy number losses in human neoplasms detected by comparative genomic hybridization. Recurrent losses that affect each of the chromosome arms in 73 tumor types are tabulated from 169 reports. The tables are available online at http://www.amjpathol.org and http://www. helsinki.fi/ approximately lglvwww/CMG.html. The genes relevant to the lost regions are discussed for each of the chromosomes. The review is supplemented also by a list of known and putative tumor suppressor genes and DNA repair genes (see Table 1, online). Losses are found in all chromosome arms, but they seem to be relatively rare at 1q, 2p, 3q, 5p, 6p, 7p, 7q, 8q, 12p, and 20q. Losses and their minimal common overlapping areas that were present in a great proportion of the 73 tumor entities reported in Table 2 (see online) are (in descending order of frequency): 9p23-p24 (48%), 13q21 (47%), 6q16 (44%), 6q26-q27 (44%), 8p23 (37%), 18q22-q23 (37%), 17p12-p13 (34%), 1p36.1 (34%), 11q23 (33%), 1p22 (32%), 4q32-qter (31%), 14q22-q23 (25%), 10q23 (25%), 10q25-qter (25%),15q21 (23%), 16q22 (23%), 5q21 (23%), 3p12-p14 (22%), 22q12 (22%), Xp21 (21%), Xq21 (21%), and 10p12 (20%). The frequency of losses at chromosomes 7 and 20 was less than 10% in all tumors. The chromosomal regions in which the most frequent losses are found implicate locations of essential tumor suppressor genes and DNA repair genes that may be involved in the pathogenesis of several tumor types.

/pdf/dna-copy-number-losses-in-human-neoplasms-1okv0p785h.pdf

DNA Copy Number Losses in Human Neoplasms

11. Cowden syndrome (gingival multiple hamartoma syndrome) 1051 12. Esophageal cancer, tylosis with (nonepidermolytic palmoplantar keratosis and Howel-Evans’ syndrome) 1052 13. Fanconi’s anemia (includes pancytopenia, Fanconi’s type) 1053 14. Gastric cancer, familial 1054 15. Hodgkin’s disease, familial 1054 16. Li-Fraumeni syndrome 1055 17. Melanoma, familial with or without dysplastic nevi (includes dysplastic nevus syndrome, familial atypical mole–malignant melanoma syndrome, and melanoma–astrocytoma syndrome) 1056

/pdf/the-concise-handbook-of-family-cancer-syndromes-2z0swsudaf.pdf

The Concise Handbook of Family Cancer Syndromes

Epidemiological data suggest the presence of a susceptibility gene for testicular cancer in some families. Families with multiple cases of testicular cancer are rare and almost all those reported have only two affected members. We have performed a sib-pair analysis on 35 families in which there are either two or three affected brothers. These families have been typed for 220 autosomal microsatellite markers spaced 10-20 cM throughout the genome. Six regions which gave a LOD score of more than 1.0 on formal linkage analysis or a P value of 0.05 or less using a non-parametric approach are considered as candidate regions for a susceptibility gene. Of particular interest is one region on chromosome 4. Two neighbouring probes in this region both scored positively with LOD score of 2.60 on multipoint analysis. An International Testis Cancer Linkage Consortium has been formed to pool resources and will investigate these findings further with the world-wide collection of families.

Candidate regions for a testicular cancer susceptibility gene

The serological recognition of HLA-D related or class II antigens dates back to an observation of Ceppellini (Ceppellini et al. 1971 a, b) that some HLA typing sera could inhibit the mixed lymphocyte reaction (MLR). This predated the identification of HLA-D antigens as defined by this cellular method (van Leeuwen et al. 1973). About the same time, it was noted that some typing sera gave extra reactions, not accounted for by their HLA class I activity, on cultured B lymphoblastoid cell lines (BCL) (Dick et al. 1972) and chronic lymphatic leukaemia cells (CLL) (Walford et al. 1973). There was much discussion at the time as to whether the antigens identified by these reactions were tumour or virally induced or whether they occurred in normal cells. When T and B lymphocytes were separated, using for example the sheep red blood cell rosetting technique (Jondal et al. 1972), the antigens were indeed found to be present on normal peripheral B lymphocytes, which usually form 10%–20% of the normal lymphocyte population.

S. Tonks

Papers

Candidate regions for a testicular cancer susceptibility gene

B Cell Recognition and HLA Typing: Current Methods and Future Possibilities. Role of Alloantibodies and Monoclonal Antibodies as Reagents