J Med Genet: first published as 10.1136/jmg.25.5.294 on 1 May 1988. Downloaded from Gene mapping and medical genetics Journal of Medical Genetics 1988, 25, 294-306 Genetic markers on chromosome 7 LAP-CHEE TSUI From the Department of Genetics, The Hospitalfor Sick Children, 555 University Avenue, Toronto, Ontario MSG 1X8, and the Departments of Medical Genetics and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. SUMMARY Chromosome 7 is frequently associated with chromosome aberrations, rearrange- ments, and deletions. It also contains many important genes, gene families, and disease loci. This brief review attempts to summarise these and other interesting aspects of chromosome 7. With the rapid accumulation of cloned genes and polymorphic DNA fragments, this chromosome has become an excellent substrate for molecular genetic studies. Chromosome 7 has been a subject of interest in gene structure analysed in detail; some have only medical genetics because of its frequent association been assigned by enzyme activities, such as bili- with chromosome aberrations, rearrangements, and verdin reductase 2 and paraoxanase.51-54 copyright. deletions, and because of the localisation of several There are several gene families identified on important genes, gene families, and disease loci on chromosome 7. The T cell receptor I6 and y chain this chromosome. It accounts for approximately 5% genes have received most of the attention in the past of the human genomel and it is estimated to be 136 few years. Both genes have complex gene structures centimorgans (cM) in length2 and to contain 150 and belong to the large immunoglobulin multigene million basepairs of DNA. The short (p) and long family.94 9 Expression of these genes requires (q) arm size ratio is approximately 1 to 1-5 (figure), proper chromosome rearrangement joining diffe- http://jmg.bmj.com/ but it varies significantly between prometaphase and rent DNA segments together during T cell midmetaphase.3 differentiation." The y chain gene has been local- Approximately 40 genetic loci were reported to be ised to the short arm, region p15.201 21 The f chain on chromosome 7 at the Eighth Human Gene gene has been mapped to 7q3 but different sub- Mapping Workshop (Helsinki, September.1985).4 5 region localisation data have been obtained by diffe- There has been a dramatic increase of markers on rent investigators; it is still unclear whether the gene this chromosome since then. The total number of maps to q3268 or q35.67 69 gene loci and DNA markers characterised now well The multidrug resistant phenotype of tumour cells on September 27, 2021 by guest. Protected exceeds 4006 (figure, table, K-H Grzeschik, 1987, is correlated with increased expression and amplifi- personal communication, L-C Tsui et al, unpub- cation of the PGY-1 (mdr-J) locus which encodes a lished data). In addition, a chromosome 7 specific membrane glycoprotein called P glycoprotein.9798 genomic library has been constructed by the Los This protein is thought to function as an energy Alamos and Lawrence Livermore National Labor- dependent export pump to reduce intracellular atories using flow sorted chromosome 7 from a levels of anticancer drugs.99 Molecular cloning and hamster-human hybrid cell line.7 mapping studies showed that the PGY-1 locus probably contains a number of related genes clustei- Genes and gene families ed within 7q21-*q22.5 4 The 1-actin'3 and the proa2(I) collagen-39-43 genes More than 35 genes of assigned functions have been also belong to multigene families but their related localised to chromosome 7. They are listed in the members are dispersed elsewhere in the genome. table. Some of the genes, such as f-actin'3 and proa2(I) collagen,39-43 have been cloned and the Disease loci to Received for publication 10 August 1987. A number of disease loci have been mapped Accepted for publication 11 August 1987. chromosome 7. The metabolic defects argininosucci- 294 J Med Genet: first published as 10.1136/jmg.25.5.294 on 1 May 1988. Downloaded from Genetic markers on chromosome 7 295 22 IPSP (mS) 21 15.3 15.2 15.1 14 13 D7S12 ASL (m5) 1213i 11:9 Q 11.23 M F 21.1 U COL1A2- 21.2 D7S1 s - 21.3 A2 EPO - 7.7 24.0 ICOL1 PON 22 (m16) IGUSB (in5) D7S13 IPGY1 2.6 7.8 31.1 D7S13 D7S15 D7S1 6- 31.2 D7S16 EPO BCP 0.4 1.3 CPA (m6) MET - _ 1.4 4.2 31.3 MET (m6) PON ERV3 CF ACTBP5 _ 0.9 2.7 CF D7S8 32 D7S8 TRYI (m6) I NM 21.5 65.8 33 TCRB (m") 34 TCRB-_ copyright. 35 BND3L I 36 7 FIGURE Genetic markers on chromosome 7. Regional localisations are indicated by vertical bars. The homologous mouse chromosomes are shown in brackets. The male andfemale genetic linkage maps for selected loci are shown on the right with numbers in centimorgans. http://jmg.bmj.com/ nicaciduria, mucopolysaccharidosis VII, and trypsi- which is a group of autosomal dominant connective nogen deficiency are probably the result of muta- tissue disorders with skeletal, cardiac, and ocular tions within the genes encoding the enzymes that are defects.'113 A 20 amino acid insertion was found in involved in the biochemical pathway, namely argini- 50% of the proa2(I) chains in one patient and was nosuccinic lyase, 3-glucuronidase, and trypsinogen, thought to be the cause of the disease.'14 DNA on September 27, 2021 by guest. Protected respectively.1l8 Tritan colour blindness probably sequence analysis of the proc2(1) collagen gene results from mutation of the blue-opsin gene.57 revealed a 38 bp insertion in this patient.'11 How- Osteogenesis imperfecta describes a group of ever, subsequent studies showed that this 38 bp fragile bone disorders which are clinically insertion is a common DNA fragment length poly- heterogeneous. 1" The syndrome can be divided into morphism among random normal subjects"'" and four phenotypic groups depending on the presence there is no linkage relationship between the disease or absence of short stature, joint laxity, easy locus and the proa2(I) collagen gene in family bruising, blue sclerae, presenile hearing loss, and studies."'7 (18 dentinogenesis imperfecta. All of these symptoms Ehlers-Danlos syndrome is another hetero- are presumed to be the result of mutations in one of geneous group of disorders with collagen defects. "(M the six collagen genes. The genetics of 01 have Their clinical manifestations include laxity of joints, recently been reviewed in this Journal. 102 The soft and extensible skin which may also be fragile, proa2(I) collagen gene which is involved in all four and excessive bruising. At least one form of this groups is located on the long arm of chromosome 7 syndrome has been proposed to result from ab- (7q21-3--*q22- 1). normal cleavage of the N-peptide of the proa2(I) The collagen genes have also been prime candi- chain."'9 dates for the gene mutation in Marfan syndrome, Cystic fibrosis (CF) is the most common severe J Med Genet: first published as 10.1136/jmg.25.5.294 on 1 May 1988. Downloaded from 296 Lap-Chee Tsui TABLE Genes and DNA probes. Regional Gene Name or probe Mode* RFLP References assignment sYmbol Genes pter- pl5 COLL5 Collagen-like 5 A 8 pter- pl4 GCTG y-glutamylcyclotransferase S 9 pter--.p22 PSP Phosphoserine phosphatase S 11) pter- yq I HIL Histone HI-like gcnes A 11 pter-.q22 NPY Neuropeptide Y S,RE 12 pter-).q22 ACTB li-actin S,RE 13 pter- q22 PDGFA Platelet derived growth RE,S 14 factor. A chain p22- 1---q2l DIA2 Diaphorase S 15, 16 p21l- pl4 HOX-1 Mouse Hox- I homologue RE,S 17 p2l-.*q22 ASL Arginosuccinate lyase S,RE 18. 19 p'5 TCRG T cell reccptor. y chain S.RE + 211, 21 pl4- cen BLVR Biliverdin reductase S.RE 22, 23 pl pI I EGFR Epidermal growth factor S 24-28 receptor (=ERBB) pl2 -pl4 ERBB v-erbB oncogene homologue S.RE 29-32 (avian crythroblastic leukaemia virus) p1.--+q22 MDH2 NAD malate dehydrogenase 33 p i--+ (mitochondrial) p1l-~l I1 ASNS Asparagine synthetasc S.RE+ 34, 35 cen-q 1 12 MYHS Myosin heavy polypeptidc. A 36 aidult skeletal muscle q2l--q22 ERV3 v-ert'3 homologue S,RE 37, Tsui et al, unpublished data q21 .3-+q22-I COLIA? Collagen. typc I o2 S,RE + 38-43 PGYI P glycoprotcin S.RE,A 44-46 GUSB 3-glucuronidase S,RE 33, 45, 47, Tsui et al, unpublished data copyright. q22 G protein, o(H subunit S,RE FS Collins, J Seidman, 1987, personal communication q22-tcq22 EPO Erythropoietin S,RE + 48-511 q22 PON Paratoxonasc F 51-54 MET met proto-oncogene RE.A.S 45, 55, 56 BCP Blue cone pigment RE.S 57 q22--*qtcr CPA Cairboxypeptidase A RE 58 q22 rqtcr ACTBPS P-actin pseudogene 5 S,RE 13 + q22 qtcr TRY I Trypsin S.RE 58, 59 http://jmg.bmj.com/ q3I CF Cystic fibrosis F 53, 60-63 q32 or q35 TCRB T cell receptor. B chakin RE.S.A + 64-69 q3S-.q36 BND3L Baind 3-like. fibroblaist RE.S + 711 ASSPI Arginosuccinatte svnthetaise RE.S + 71, 72 pseudogenc I PAI-I Plhtsminogcn itctiv;dtor S,RE 73 inhibitor Cytochrome P450( protein S,RE + 74 glucocorticoid inducibie INFB2 P2 interferon SRE + 75 UP Uridine phosphorylavse S 76 on September 27, 2021 by guest. Protected HADH Hydroyvtcyl-CoA dchydrogcn;ise S 77 P04DB Procollagen-proline. 2-oxogluta- S 78 rate: 4-dioxygenase. 3 chatin DNA segot(ntcs pter-pl4 D7SIO p.1511 RE.S + 79 pter-.q22 D7S/ I Phtgc f( RE.S+ 211 ptcr-q22 D7.S12 pB78 RE.S 79.810 pI2-qtcr DNF9 pA-8 81 pll--q II !37Zl Chromosome 7 specific RE.S+ 82.