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J Med Genet: first published as 10.1136/jmg.24.11.649 on 1 November 1987. Downloaded from e-one mapping and medical genetics Journal of Medical Genetics 1987, 24, 649-658 The molecular genetics of human chromosome 6 VINCENT CUNLIFFE AND JOHN TROWSDALE From the Human Immunogenetics Laboratory, Imperial Cancer Research Fund, PO Box 123, Lincoln's Inn Fields, London WC2A 3PX. SUMMARY Chromosome 6 contains several clinically important markers as well as classical enzyme loci, proto-oncogenes, and a growing number of anonymous DNA restriction fragment length polymorphisms (RFLPs). It is also of unique interest because of the location of the major histocompatibility complex (MHC) on the short arm, at 6p21-3. The MHC is one of the most detailed areas of the human genetic map to date and many important diseases, some of a sus- pected autoimmune aetiology, are associated with it. General Fragile About 70 well characterised genetic loci have been markers sites RFLP r mapped to human chromosome 6 (fig 1). Consider- vI 25 copyright. able interest has been focused on those of the HLA 24 system, located on the short arm at 6p213. This 23 I PYHGS UF12 TUBB multigene complex, otherwise termed the major >>FR A 6A 2222-3 histocompatibility complex (MHC), encodes class I p 22.1 I. D6S7 and class II HLA molecules as well as some com- IHLA 21.3 , _D6S8IS 9 plement components and is involved in defence 21.2 PIMG I KRAS 11 D659 I I against a variety of diseases. Particular alleles of 21.1 GLOK PRL D6S101 some HLA loci are associated with hereditary pre- 12 MERM1lG dispositions to diseases, for example, insulin depen- 1: http://jmg.bmj.com/ dent diabetes mellitus (IDDM), narcolepsy, anky- 13 IMEI 6DS5 losing spondylitis, rheumatoid arthritis, and Hodg- 13 PGM3 *FRA6 14 D6S11 kin's lymphoma. The HLA complex spans over 3 x 15 GA 106 bp and to date contains more than 20 expressed 16.1 Ic genes. The considerable knowledge that has accum- 16-3 I ulated concerning the organisation, structure, 21 SOD2 regulation, and functions of the q I genes in this linkage 22-1 on September 30, 2021 by guest. Protected group forms a paradigm for studies of the molecular 22.2 biology of a complex region of the human genome 22.3 MYB D6S1 and- it will be covered in detail in this article. 23.3 Chromosome 6 is already known to encode a large 24 number of enzyme and surface antigen loci, several proto-oncogenes, and at least six pseudogenes, four I TCP * FRA 6B of which have been assigned close to, or within, the HLA In 27 region. addition, there are several fragile 6 PLG sites involved in translocations, inversions, and dele- tions which are aetiologically linked to some lym- FIG I Regionally localised markers on human I chromosome 6. Thisfigure is mostly based on data collated phoid and other malignancies. The genetic markers in the 8th Human Gene Mapping Workshop. The of chromosome 6 are summarised in fig 1 and are HLA complex is shown in detail in fig 2 and the markers are referenced in the table. explained in the table. Vertical bars indicate the Received for publication 18 May 1987. (approximate) extents ofthe boundaries within which Accepted for publication 21 May 1987. a particular marker is located. 649 J Med Genet: first published as 10.1136/jmg.24.11.649 on 1 November 1987. Downloaded from 650 Vincent Cunliffe and lb Trowsdale TABLE Markers oni chromosome 6. Getne sYmbol Locationi Descriptioni Reference anid remark-s ADCP 6 Adenosine de.tminase compiexing protein I 1. 17 ARGI 6 Arginase. lister 15. 62 ASSP2 6 Argininosuccinaite svnthetase pscudogene 2 4. 5. 31. 32 BEVI 6 Baboon M7 sirus integration site 6. 84 BKMAI 6q2l Banded krait minor satellite DNA-I 85. 101 CA21HA 6p2l 3 Congenital adrenal hyperplasia (21 -hydroxylase deficiency) A HLA region. CA21 HB 6p2l '3 Congenital adrenal hvperplasia (21-hydroxylase deficiency) B see fig 2 CGA 6q12-q2l Chorionie gonadotrophin. Ct polypeptide 45. 85 cscI 6 Corticosterone sideehain isomerase 42-44. 82-84 D6S7 6p2 l-pter Anonymous DNA segment from p7H4 19. 83 D6S8 (6p2l Anonymous DNA segment from p2C5 18. 83 DHFRP2 6 Dthvdrofolate reductase pseudogene 2 34. 77 ER 6 Oestrogen receptor 17. 59. 60, 98 F12 6p23 Clotting factor XII (Hageman factor) 14. 15. 47. 48 F13A 6pl3--qter Clotting factor XIII. A subunit 16 FEA 6 Fg embrvonic antigen 14. 92 FRA6A (sp23 Fragile site, folic acid type. rtre. fra(6)(p23) 12. 72 FRA6B 6p25.1 otr 6q216 Fragile site, aphidicolin type. common. fra(6)(q25l1 or q26) 12. 72 FRA6C 6p22.2 Fragile sitet aphidicolin type, common. fra(6)(p222) 12. 72 FRA6D 6q 13 Fragile site, aphidicolin type, common. fra(6)(ql3) 12. 72 FTHL 6mp2l -3-~pl2 Ferritin-like sequence. heavy polvpeptide 12. 87. may be in HLA region. see note, fig 2 FUCA2 6 Ct- l-fucosidase2 13. 49 GLO I 6p2l 2I-.p2 1i Glyoxalase I 6-8. 17- 19 HFE 6sp2l1.3 Ha1emochromaitosis 211 88. may be in HLA region. strongly associated with HLA-A. see fig 2 HLA and comple- ment components C2' C4. BF bp2 13 See detailed map. fig 2 1. 44. 91 (this contains a discussion of HLA class I. class II. and class III genes and diseases associated with the region) 61 INFR 6q ct interferon receptor 57. copyright. INSL 6p23--q12 Insulin-like sequence. AGB6 38. 78 KRASI 6p23--ql2 Proto-oncogenes. c-Ki-ras- I processed pseudogene 21-23. 35-37 LQT 6 I.ong 0T (Romano-Ward syndrome) 24. 93 MEI 6q 12 Malic enzvme 1. soluble 11. 25 ME2 6 Mailic enzvme 2. mitochondrial 1(). 26 MCF3 6q 16- q2-2 Proto-oncogene MCF-3 71. 102 MRBC 6 Monkey red blood cell receptor 27. 57 MSK28 6 Antigen identified by monoclonail antibody MG2 28. 53 MSK29 6 Antigen identified by monocionail antibody A42 28. 53 MYB hql45-q4 Asian myeloblastosis viral (v-mnrh) oncogene homologue 13. 29-31. 67-7(1 NDF 6 Neutrophil differentiation faictor 15. 94 NEU 6p2 1.3 Ncuraminidaise 1 sialitosis 15. 91) http://jmg.bmj.com/ p 6 P blood group (globoside) 32. 33. 55. 56 PGKIP2 6p2l- pl2 Phosphoglvcerate kinase 1. pscudogene 2 2(1 28-3(1. 34. 35. 102 PGM3 6q 12 Phosphoglucomutase 3 12. 13. 37. 38 PIM Proto-oncogene pint 54. 56. 64 65 PLG 6p25.-qter Plasminogen 39. 4(1. 5(). 51 PRL 6p3-~q12 Prolactin 39. 79 PUTI 6 Polypeptide m44p in lymphocyte membraine 42. 52 PYHG5 bpter-p2I Protein spot in 2D gels (MWN' 90K) 43. 95 ROS 6q16-.ql2 Proto-oncogecne ros 59. 63 RPL32P bp2 13 Ribosomal protein L32 pseudogene 33. 76 SCA 6 Spinocerebellar ataxia 45. 46. 80. 81 on September 30, 2021 by guest. Protected SOD2 6q2 Superoxide dismutase 2. mitochondrial 14. 61 SRBC 6 Sheep red blood cell receptor 48. 58. M Brown. personal communication. 1987 S5 6 Surface antigen 5 (MW 45KD) 49. 54 TCPI 6q23-'-qter T complex polypeptide I 5. 24. 103 TNFA 6p2-3--q12 Tumour necrosis factor a 18. 78. 79. 97 TNFB Tumour necrosis factor )5. lymphotoxin } TRM I 6p2.3--ql12 Methionine tRNA initiator I 5 TRM2 6p23-~qI12 Methioninc tRNA initiator 2 TS546 6 Temperature sensitivity complcmentation. ts546 19. 97 TUBB 6pter-.p2 tubulin 4. 52 YES2 6 Yamaguchi satrcoma viral )v-vt-s-2) oncogene homologue 2 53. 66 Correlating the formal genetic map with the along human chromosomes undergoing meiosis at molecular genetic map of chromosome 6 the pachytene stage. Using data taken from a large number of chromosomes they constructed a map Morton et a12 mapped the distribution of chiasmata which charted the frequenicy of crossovers per unit J Med Genet: first published as 10.1136/jmg.24.11.649 on 1 November 1987. Downloaded from Gene mappinv- id medical genetics 651 length of ch1 - - ome. On chromosome 6 this some substance to the notion of a human equiva- frequency was-ui,- variable, particularly near the lent. 24 centromere and, therefore, inconsistencies between In view of this, and the restricted expression of the molecular map and the formal genetic map are the human and mouse isoenzymes to the testis,27 it to be expected. seemed plausible that this human PGK locus might T'Iere are estimated to be about 52 chiasmata per be linked to HLA. A human genomic clone was iso- human meiosis. The genetic length of the human lated containing PGK sequences and mapped to autosomes is therefore 52/2 x 100 = 2600 cM (divi- 6p23-*p12.28 However, sequence analysis of this sion by two is necessary because only two of the four DNA identified a PGK processed pseudogene strands in a bivalent are involved in the chiasma; (PGKIP2) lacking all introns, flanked by 11 nucleo- multiplication by 100 gives the length in centi- tide direct repeats, punctuated by a premature in morgans). Chromosome 6 was estimated to consti- frame termination codon.29 Recent evidence from tute 2.5% of the total autosome length of 2600 cM, a different source has indicated that the intron-less that is, 65 cM.2 However, Francke and Pellegrino3 PGK2 gene has a complete open reading frame and estimated that chromosome 6 made up more a testis specific pattern of expression.10 As such it like 6% of the haploid complement, which gives a would be a rare example of a functional processed much greater value of 150 cM. In the next few years, cellular (pseudo)gene. It is likely that both groups as more RFLP data accumulate, it will be possible to have studied the same genomic locus and, if this is generate detailed molecular maps of sections of so, discrepancies between their sequences have yet chromosome which are saturated with markers.
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  • 12Q Deletions FTNW

    12Q Deletions FTNW

    12q deletions rarechromo.org What is a 12q deletion? A deletion from chromosome 12q is a rare genetic condition in which a part of one of the body’s 46 chromosomes is missing. When material is missing from a chromosome, it is called a deletion. What are chromosomes? Chromosomes are the structures in each of the body’s cells that carry genetic information telling the body how to develop and function. They come in pairs, one from each parent, and are numbered 1 to 22 approximately from largest to smallest. Additionally there is a pair of sex chromosomes, two named X in females, and one X and another named Y in males. Each chromosome has a short (p) arm and a long (q) arm. Looking at chromosome 12 Chromosome analysis You can’t see chromosomes with the naked eye, but if you stain and magnify them many hundreds of times under a microscope, you can see that each one has a distinctive pattern of light and dark bands. In the diagram of the long arm of chromosome 12 on page 3 you can see the bands are numbered outwards starting from the point at the top of the diagram where the short and long arms meet (the centromere). Molecular techniques If you magnify chromosome 12 about 850 times, a small piece may be visibly missing. But sometimes the missing piece is so tiny that the chromosome looks normal through a microscope. The missing section can then only be found using more sensitive molecular techniques such as FISH (fluorescence in situ hybridisation, a technique that reveals the chromosomes in fluorescent colour), MLPA (multiplex ligation-dependent probe amplification) and/or array-CGH (microarrays), a technique that shows gains and losses of tiny amounts of DNA throughout all the chromosomes.