The same markers in the marsupial Monodelphis domestica (gray short-tailed opossum) span 3.95 Mb and contain 114 genes, 87 shared with humans.

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1 The major histocompatibility complex (MHC) is a large genomic region or gene family found in most vertebrates that encodes MHC molecules. MHC molecules play an important role in the immune system and autoimmunity In humans, the 3.6-Mb ( base pairs) MHC region on chromosome 6 contains 140 genes between flanking genetic markers MOG and COL11A2. About half have known immune functions. The same markers in the marsupial Monodelphis domestica (gray short-tailed opossum) span 3.95 Mb and contain 114 genes, 87 shared with humans. 國 立 交 通 大 學 生 物 資 訊 及 系 統 生 物 研 究 所 林 勇 欣 老 師 x MHC Sequencing Consortium (1999) Nature Belov et al. (2006) PLoS Biology

2 Name Function Expression MHC class I MHC class II Encodes non-identical pairs (heterodimers) of peptide-binding proteins, as well as antigen-processing molecules such as TAP and Tapasin. Encodes heterodimeric peptidebinding proteins and proteins that modulate antigen loading onto MHC class II proteins in the lysosomal compartment such as MHC II DM, MHC II DQ, MHC II DR, and MHC II DP. All nucleated cells. MHC class I proteins contain an αchain & β2-micro-globulin(notpart of the MHC encoded by chromosome 15). They present antigen fragments to cytotoxict-cells via the CD8 receptor on the cytotoxict-cells and also bind inhibitory receptors on NK cells. On most immune system cells, specifically on antigen-presenting cells. MHC class II proteins contain α& βchains and they present antigen fragments to T-helper cells by binding to the CD4 receptor on the T-helper cells. MHC class III region Encodes for other immune components, such as complement components (e.g., C2, C4, factor B) and some that encode cytokines (e.g., TNF-α) and also hsp. Class III has a function very different from that of class I and class II, but, since it has a locus between the other two (on chromosome 6 in humans), they are frequently discussed together. 國 立 交 通 大 學 生 物 資 訊 及 系 統 生 物 研 究 所 林 勇 欣 老 師 x

3 The best-known genes in the MHC region are the subset that encodes antigen-presenting proteins on the cell surface. In humans, these genes are referred to as human leukocyte antigen (HLA) genes; however people often use the abbreviation MHC to refer to HLA gene products. To clarify the usage, some of the biomedical literature uses HLA to refer specifically to the HLA protein molecules and reserves MHC for the region of the genome that encodes for this molecule. This convention is not consistently adhered to, however. 國 立 交 通 大 學 生 物 資 訊 及 系 統 生 物 研 究 所 林 勇 欣 老 師 x

4 The most intensely studied HLA genes are the nine so-called classical MHC genes: HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA- DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, and HLA-DRB1. In humans, the MHC is divided into three regions: Class I, II, and III. The A, B, C, E, F, and G genes belong to MHC class I, whereas the six D genes belong to class II. 國 立 交 通 大 學 生 物 資 訊 及 系 統 生 物 研 究 所 林 勇 欣 老 師 x

5 Human leukocyte antigen (HLA) PDB ID: 1AKJ chain A 國 立 交 通 大 學 生 物 資 訊 及 系 統 生 物 研 究 所 林 勇 欣 老 師

6 The object of this course is collecting the nucleotide (or mrna) sequences of HLA genes from human and other species (focus on class I MHC; but not class II MHC) Human Chimp others HLA-A PATR-A : HLA-B PATR-B : HLA-C : : HLA-E : : HLA-F : : HLA-G : : etc etc etc Go to NCBI ( Practice using the resources provided on NCBI, e.g., Gene, Nucleotide, BLAST, HomoloGene, etc, to collect these sequences Save them using FASTA format in your computer 國 立 交 通 大 學 生 物 資 訊 及 系 統 生 物 研 究 所 林 勇 欣 老 師

7 FASTA format: >gi ref NM_ Homo sapiens major histocompatibility complex, class I, A (HLA-A), mrna ATGGCCGTCATGGCGCCCCGAACCCTCCTCCTGCTACTCTCGGGGGCCCTGGCCCTGACCCAGACCTGGG CGGGCTCCCACTCCATGAGGTATTTCTTCACATCCGTGTCCCGGCCCGGCCGCGGGGAGCCCCGCTTCAT CGCCGTGGGCTACGTGGACGACACGCAGTTCGTGCGGTTCGACAGCGACGCCGCGAGCCAGAGGATGGAG CCGCGGGCGCCGTGGATAGAGCAGGAGGGGCCGGAGTATTGGGACCAGGAGACACGGAATGTGAAGGCCC AGTCACAGACTGACCGAGTGGACCTGGGGACCCTGCGCGGCTACTACAACCAGAGCGAGGCCGGTTCTCA CACCATCCAGATAATGTATGGCTGCGACGTGGGGTCGGACGGGCGCTTCCTCCGCGGGTACCGGCAGGAC GCCTACGACGGCAAGGATTACATCGCCCTGAACGAGGACCTGCGCTCTTGGACCGCGGCGGACATGGCGG CTCAGATCACCAAGCGCAAGTGGGAGGCGGCCCATGAGGCGGAGCAGTTGAGAGCCTACCTGGATGGCAC GTGCGTGGAGTGGCTCCGCAGATACCTGGAGAACGGGAAGGAGACGCTGCAGCGCACGGACCCCCCCAAG ACACATATGACCCACCACCCCATCTCTGACCATGAGGCCACCCTGAGGTGCTGGGCCCTGGGCTTCTACC CTGCGGAGATCACACTGACCTGGCAGCGGGATGGGGAGGACCAGACCCAGGACACGGAGCTCGTGGAGAC CAGGCCTGCAGGGGATGGAACCTTCCAGAAGTGGGCGGCTGTGGTGGTGCCTTCTGGAGAGGAGCAGAGA TACACCTGCCATGTGCAGCATGAGGGTCTGCCCAAGCCCCTCACCCTGAGATGGGAGCTGTCTTCCCAGC CCACCATCCCCATCGTGGGCATCATTGCTGGCCTGGTTCTCCTTGGAGCTGTGATCACTGGAGCTGTGGT CGCTGCCGTGATGTGGAGGAGGAAGAGCTCAGATAGAAAAGGAGGGAGTTACACTCAGGCTGCAAGCAGT GACAGTGCCCAGGGCTCTGATGTGTCCCTCACAGCTTGTAAAGTGTGAGACAGCTGCCTTGTGTGGGACT GAGAGGCAAGAGTTGTTCCTGCCCTTCCCTTTGTGACTTGAAGAACCCTGACTTTGTTTCTGCAAAGGCA CCTGCATGTGTCTGTGTTCGTGTAGGCATAATGTGAGGAGGTGGGGAGACCACCCCACCCCCATGTCCAC CATGACCCTCTTCCCACGCTGACCTGTGCTCCCTCCCCAATCATCTTTCCTGTTCCAGAGAGGTGGGGCT GAGGTGTCTCCATCTCTGTCTCAACTTCATGGTGCACTGAGCTGTAACTTCTTCCTTCCCTATTAAAATT AGAACCTTAGTATAAATTTACTTTCTCAAATTCTTGCCATGAGAGGTTGATGAGTTAATTAAAGGAGAAG ATTCCTAAAATTTGAGAGACAAAATAAATGGAACACATGAGAACCTTCCAAAAAAAAAAAAAAAAAAA >gi ref NM_ Pan troglodytes major histocompatibility complex, class I, A (PATR-A), mrna ATGGCCGTCATGGCGCCCCGAACCCTCGTCCTGCTACTCTCGGGGGCCCTGGCCCTGACCCAGACCTGGG CGGGCTCCCACTCCATGAGGTATTTCTCCACATCGGTGTCCCGGCCCGGCCGCGGGGAGCCCCGCTTCAT CGCCGTGGGCTACGTGGACGACACGCAGTTCGTGCGGTTCGACAGCGACGCCGCGAGCCAGAGGATGGAG CCGCGGGCGCCGTGGATAGAGCAGGAGGGTCCGGAGTATTGGGACGAGGAGACACGGAGTGTGAAGGCCT CCGCACAGACTGACCGAGTGGACCTGGGGACCCTGCGCGGCTACTACAACCAGAGCGAGGACGGTTCTCA CACCATCCAGTTAATGTTTGGCTGCGACGTGGGGTCGGACGGGCGCTTCCTCCGCGGGTACCGGCAGGAC GCCTACGACGGCAAGGATTACATCGCCCTGAACGAGGACCTGCGCTCTTGGACCGCGGCGGACATGGCGG CTCAGATCACCCAGCGCAAGTGGGAGGCGGCCCATGCGGCGGAGCAGCTGAGAGCCTACCTGGAGGGCAC GTGCGTGGAGTGGCTCCGCAGATACCTGGAGAACGGGAAGGAGACGCTGCAGCGCACTGACCCCCCCAAG ACACATATGACCCACCACCCCATCTCCGACCGTGAGGCCACCCTGAGGTGCTGGGCCCTGGGCTTCTACC CTGCGGAGATCACACTGACCTGGCAGCGGGATGGGGAGGACCAGACCCAGGACACGGAGCTCGTGGAGAC CAGGCCTGCAGGGGATGGAACCTTCCAGAAGTGGGCAGCTGTGGTGGTACCTTCTGGAGAGGAGCAGAGA TACACCTGCCATGTGCAGCATGAGGGTCTGCCCAAGCCCCTCACCCTGAGATGGGAGCCGTCTTCCCAGC CCACCATCCCCATCGTGGGCATCATTGCTGGCCTGGTTCTCCTTGGAGCTGTGATCACTGGAGCTGTGGT CGCTGCCGTGATGTGGAGGAGGAAGAGCTCAGATAGAAAAGGAGGGAGCTACTCTCAGGCTGCAAGCAGT GACAGTGCCCAGGGCTCTGATGTGTCTCTCACAGCTTGTAAAGTGTGAGACAGCTGCCTTGTGTGGGACT GAGAGGCAAGAGTTGTTCCTGCCCTTCCCTTTGTGACTTGAAGAACCCTGACTTTGTTTCTGCAAAGGCA CCTGCATGTGTCTGTGTTCTTGTAGGCATAATGTGAGGAGGTGGGGAGACCACCCCACCCCCATGTCCAC CATGACCCTCTTCCCACGCTGACCTGTGCTCCCTCCCCAATCATCTTTCCTGTTCCAGAGAGGTGGGGCT GAGGTGTCTCCATCTCTGTCTCAACTTCATGGTGCACTGAGCTGTAACTTCTTCCTTCCCTATTAAAATT AGAACCTGAGTATAAATTTACTTTCTCAAATTCTTGCCATGAGAGGTTGATGAGTTAATTAAAGGAGAAG ATTCCTAAAATTTGAGAGACAAAATAAATGGAACCACATGAG 國 立 交 通 大 學 生 物 資 訊 及 系 統 生 物 研 究 所 林 勇 欣 老 師

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21 Homework: Collect the coding sequences of the HLA class I family, and their homologous sequences in other species. Build a fasta file (*.fas). Use MEGA to perform a multiple sequences alignment and export a MEGA file (*.meg). Also collect the coding sequences of the mitochondrial cytochrome b genes from as many species as you like, and perform the alignment and export a MEGA file. 國 立 交 通 大 學 生 物 資 訊 及 系 統 生 物 研 究 所 林 勇 欣 老 師