Summarize the following scientific literature


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do not copy from the paper and use your own words!!! Summarize it using your own words!

i need minimum 600 words for the summary. include all the requirements below!

plagiarism is not allowed. should use own words

  1. Read the paper from the primary scientific literature assigned to your lab section. Write a few paragraphs summarizing the paper. Write in full sentences with attention to spelling, grammar, and good writing style. Write the summary in your own words; do not copy and paste from the paper or use quotes. Be sure to include the following in your paragraph.
  1. Background information (4 pts.)
  2. The authors’ purpose/goal/question (4 pts.)
  3. Brief methodology (4 pts.)
  4. Results of the study (4 pts.)
  5. Conclusions (4 pts.)

Do not copy from the paper or the internet or it will n\be considered plagiarism.

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Tissue Antigens ISSN 0001-2815 The distribution of major histocompatibility complex class I polymorphic Alu insertions and their associations with HLA alleles in a Chinese population from Malaysia D. S. Dunn1, M. K. Choy2, M. E. Phipps2 & J. K. Kulski1,3 1 Centre for Comparative Genomics, School for Information Technology, Murdoch University, Murdoch, Western Australia, Australia 2 Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia 3 Division of Molecular Life Science, Department of Genetic Information, School of Medicine, Tokai University, Isehara, Kanagawa, Japan Key words Alu; dimorphism; haplotype; human leucocyte antigen-A alleles; major histocompatibility complex Correspondence Jerzy K. Kulski, PhD Centre for Comparative Genomics School for Information Technology Murdoch University Murdoch Western Australia 6150 Australia Tel: 161 8 9360 2492 Fax: 161 8 9360 7238 e-mail: Received 27 November 2006; revised 12 April 2007; accepted 8 May 2007 doi: 10.1111/j.1399-0039.2007.00868.x Abstract The frequency and association of polymorphic Alu insertions (POALINs) with human leucocyte antigen (HLA) class I genes within the class I genomic region of the major histocompatibility complex (MHC) have been reported previously for three populations: the Australian Caucasian, Japanese and north-eastern Thai populations. Here, we report on the individual insertion frequency of the five POALINs within the MHC class I region, their HLA-A and HLA-B associations, the POALIN haplotype frequencies and the HLA-A/POALIN four-loci haplotype frequencies in the Malaysian Chinese population. The phylogenetic relationship of the four populations based on the five POALIN allele frequencies was also examined. In the Malaysian Chinese population, the POALIN AluyHG was present at the highest frequency (0.560), followed by AluyHJ (0.300), AluyMICB (0.170), AluyTF (0.040) and AluyHF (0.030). The most frequent five-loci POALIN haplotype of the 16 inferred haplotypes was the AluyHG single insertion haplotype at a frequency of 0.489. Strong associations were present between AluyHJ and HLA-A24, HLA-A33 and HLA-A11 and between AluyHG and HLA-A2, HLA-A24 and HLA-A11, and these were reflected by the inferred haplotype frequencies constructed from the combination of the HLA-A locus and the AluyHG, AluyHJ and AluyHF loci. The strongest association of AluyMICB was with the HLA-B54 allele (five of five), whereas the associations with the other 17 HLA-B alleles were weak, moderate or undetermined. Phylogenetic analysis of the five POALIN allele frequencies places the Malaysian Chinese closest to the Japanese and north-eastern Thai populations in the same cluster and separate to the Australian Caucasian population. The MHC POALINs are confirmed in this study to be informative genetic markers in lineage (haplotype) analysis, population genetics and evolutionary relationships, especially in studying the MHC genomic region. Introduction At least half of the human genome sequence is composed of repeat elements, with the Alu family contributing to 10% of the genomic content (1). The name ‘Alu element’ was given to these repeated sequences because members of this family of repeats contain a recognition site for the restriction enzyme ‘AluI’ (2). Alu elements are the most abundant class of short interspersed repeat elements 136 (SINEs) in the human genome and are sequences approximately 300 bp in length derived from the 7SL RNA gene (1). These SINEs are inserted into chromosomal DNA at different locations by retrotransposition, a mechanism in which a complementary DNA generated by reverse transcription of RNA transcripts expressed by one of a possible 100 Alu master copy sequences is then inserted into a new position in the genome (3). Polymorphic Alu ª 2007 The Authors Journal compilation ª 2007 Blackwell Munksgaard  Tissue Antigens 70, 136–143 D. S. Dunn et al. insertions (POALINs) are dimorphic structures or alleles that are either present or absent at a single site, and their ancestral state is identical in that there is no insertion. Almost all the previously inserted Alu elements are now firmly fixed within the human genome, and the generations of new Alu insertions by retrotransposition are rare events (4). Less than 0.5% of the Alu elements are reported to be polymorphic in human beings (4), and their allele frequency distribution varies in geographically distinct human populations (5), demonstrating the paucity of new Alu insertional activities. These important attributes make POALINs excellent population genetic markers, and population studies have been conducted on a large number of geographical groups using only a few or up to 100 POALIN loci distributed randomly within the whole genome (6, 7). The major histocompatibility complex (MHC) class I region in human beings is located on chromosome 6 (6p21.3), and it is characterized by the presence of the human leucocyte antigen (HLA) classical class I genes that are important in the regulation of the immune response system and in transplantation medicine (8, 9). This genomic region also has HLA non-classical class I genes and many other immunity-related expressed genes, pseudogenes, expressed sequence tag-matched sequences and sequence tag site markers (10, 11). In addition, five novel POALINs were identified within the MHC class I region and their diversity studied in Australian Caucasian and Japanese populations (12–15) and a north-eastern Thai population (16). While gathering data on the genetic diversity of the individual POALINs in different populations is of interest, it is also important to understand the haplotypic nature of these POALINs in association with their respective HLA alleles. Many researchers have reported on the large number of disease associations with HLA alleles, even though most of the associations are not absolute (<100%) (11). Many of these disease associations are most probably the result of a ‘hitchhiking’ effect of closely related genomic regions (haplotype) (17). Also, some haplotypes that were previously defined solely on the basis of matched HLA alleles were shown to be different when they were also typed for non-HLA alleles (18). We can now investigate the genetic diversity and the strength of conserved blocks within the MHC class I haplotypes by examining POALIN and HLA allelic combinations. We have already shown that multiple forms of the Japanese HLA-B48 haplotype are possible based on the presence or absence of the POALIN AluyMICB (19) and that the most common POALINcontaining haplotypes are usually those that have only one POALIN. Here, we report on the individual insertion frequencies of the five POALINs within the MHC class I region, the POALIN associations with HLA-A and HLA-B and their POALIN haplotype frequencies in a Chinese population ª 2007 The Authors Journal compilation ª 2007 Blackwell Munksgaard  Tissue Antigens 70, 136–143 MHC class I POALINs in a Chinese population from Malaysia as well as the phylogenetic relationships of four populations (Australian Caucasian, Japanese, northeastern Thai and Malaysian Chinese) based on the POALIN allele frequencies. Materials and methods Genomic DNA Peripheral blood was drawn from 50 unrelated healthy Malaysian Chinese individuals following standard procedures and after ethics approval from the Medical Ethics Committee of the University Malaya Medical Centre (UMMC) (RN #357.5). DNA was extracted and samples were diluted to a concentration of 20 ng/ml, and 1 ml was used for each polymerase chain reaction (PCR) assays. HLA-A and HLA-B genotypes data were obtained previously for the 50 individuals (20). POALIN PCR assays The PCR assays for the various POALINS were the same as those described in previous reports (12–16). The presence and/or absence of the Alu at each of the five loci were distinguished from each other by the different sizes of the PCR product for each primer pair. Briefly, the PCR solution (20 ml) contained 20 ng of template DNA, 5 pmol of each primer, 2.5 nmol of each deoxyribonucleotide triphosphates (dNTPs), 0.5–1.0 unit of AmpliTaq polymerase (Applied Biosystems, Foster City, CA) and 3 mM MgCl2 in 10 mM Tris–HCl buffer, pH 8.3. PCR was performed using a Perkin Elmer 2700 Thermal cycler programmed for 35 cycles with a denaturation (96C – 30 s), annealing (68C for AluyMICB, 62C for other – 45 s) and extension (72C – 45 s) step at each cycle. The reaction products were analysed by horizontal gel electrophoresis in 2% agarose using Tris–borate– ethylenediamine tetraacetic acid (EDTA) running buffer. Fragments of different sizes were produced for either the presence or the absence of the POALIN – a single fragment of different sizes for the two homozygous and two fragments for the heterozygous samples. Two DNA samples from the International Histocompatibility Workshop panel were used as controls, one homozygous for the absence and the other homozygous for the presence of Alu insertions. Mixtures of the two controls were also included as heterozygous controls with each PCR run. Figure 1B shows an example of the POALIN PCR products. Calculation of frequency and statistical analysis Allele frequencies were calculated using the following formula: AF ¼ sum of each individual allele/2N, where ‘N’ equals the total number of individuals and ‘AF’ represents the allele frequencies. A Hardy–Weinberg equilibrium test was performed for each of these POALINs. Heterozygosity 137 D. S. Dunn et al. MHC class I POALINs in a Chinese population Figure 1 (A) Map of the location of the five POALINs within the major histocompatibility complex class I region and (B) the amplification products of the five POALIN polymorphic chain reaction assays. MW, molecular weight; POALIN, polymorphic Alu insertions. (H) (21) was estimated as 1 2 (p2 1 q2), where ‘p’ and ‘q’ are the allele frequencies. The Expectation–Maximization algorithm in the Arlequin computer program (22) was used with parameter settings as previously described (23) to construct inferred haplotypes and to estimate the haplotype frequencies and Hardy–Weinberg equilibrium of haplotypes for the five-loci POALIN haplotypes, three-loci POALIN haplotypes in the class I alpha block and fourloci HLA-A/POALIN haplotypes (HLA-A plus the threeloci POALIN haplotypes) of the alpha block. HLA associations were estimated by calculating the proportion of individuals sharing the same HLA allele and an Alu insertion. Linkage disequilibrium was represented as the delta measurement (24) and defined as (pA 2 pB)/(1 2 pB), where ‘pA’ and ‘pB’ were the frequencies of the two alleles (HLA and POALIN) tested for association. When a negative delta value was obtained, a rearrangement of the variables was applied, and the delta prime (delta#) value was calculated as defined by (pB 2 pA)/(1 2 pA). Significance of the differences between the haplotype frequencies for the Chinese, Japanese and Australian Caucasian populations were determined by the contingency test and the Fisher’s exact test. Phylogenetic analysis Allele frequencies of the five POALINs for the Chinese in this study, Japanese and Australian Caucasians (15) and north-eastern Thai (21) were used to determine the Nei genetic distance values (25) with GENDIST in the PHYLIP (v3.5) package ( phylip/versions.html). The distance matrix was converted to 138 the MEGA format and a neighbour-joining phylogenetic tree constructed in MEGA version 2.0 (26). Bootstrap (1000 replicates; seed ¼ 64,238) values were selected to indicate the reliability of the tree topology. DisPan (Genetic Distance and Phylogenetic Analysis) was also used to confirm the phylogeny ( Results Location of POALINs within the MHC class I region A map of the location of the five POALINs and their HLA class I genes within the MHC class I region as previously determined (11, 27) is shown in Figure 1A. Essentially, AluyMICB is located within the first intron of the MICB gene in the beta block, AluyTF is located in the region between the beta and kappa blocks close to the TFIIH and CDSN genes and the remaining three elements are located within the alpha block, with AluyHJ, AluHG and AluyHF close to HLA-J, HLA-G and HLA-F, respectively. Distribution of POALIN allele frequencies in Malaysian Chinese population The observed genotypes and allele frequencies of the five POALINs are listed in Table 1. The most frequent POALIN was the AluyHG*2 allele (0.560) and the least frequent was AluyHF*2 (0.030). None of the five POALINs deviated from the Hardy–Weinberg equilibrium. The frequencies for 16 inferred five-loci POALIN haplotypes were determined by the Arlequin computer program (data not shown). The most frequent five-loci POALIN haplotype was the AluyHG single insertion ª 2007 The Authors Journal compilation ª 2007 Blackwell Munksgaard  Tissue Antigens 70, 136–143 D. S. Dunn et al. MHC class I POALINs in a Chinese population Table 1 Observed genotypes, allele frequencies, Hardy–Weinberg significance and heterozygosity for AluyMICB, AluyTF, AluyHJ, AluyHG and AluyHF in a Malaysian Chinese population (n ¼ 50) Genotypesa AluyMICB AluyTF AluyHJ AluyHG AluyHF a Allele frequencies 1,1 1,2 2,2 Aluy*1 Aluy*2 w2 P Heterozygosity (H) 34 46 23 10 47 15 4 24 24 3 1 0 3 16 0 0.830 0.960 0.700 0.440 0.970 0.170 0.040 0.300 0.560 0.030 0.199 — 1.020 0.034 — 0.66 — 0.31 0.85 — 0.282 0.077 0.420 0.493 0.058 Genotypes: 1,1, homozygote absent; 1,2, heterozygote; 2,2, homozygote present. haplotype at a frequency of 0.489 [standard deviation (SD) 0.059], followed by the AluyHJ single insertion haplotype (0.134, SD 0.032) and then the haplotype with no Alu insertions (0.123, SD 0.028). The most frequent haplotype with multiple Alu insertions contained the AluyMICB and AluyHJ insertions (0.102, SD 0.027). Three-loci POALIN haplotypes within the alpha block The 320-kb DNA segment of the MHC class I region that harbours the HLA-A, HLA-G and HLA-F genes as well as the pseudogenes HLA-J, HLA-16, HLA-80, HLA-90, HLA-H and HLA-95 have been dubbed the alpha block in this and a number of other studies (28, 29). The alpha block also contains the AluyHJ, AluyHG and AluyHF loci, which are near the HLA-J, HLA-H and HLA-F loci, respectively (12, 14–16). The three-loci haplotypes were constructed from the three Alu elements AluyHJ–AluyHG–AluyHF. Table 2 lists the haplotype identification (A–H) and haplotype definition (POALIN allelic state), the observed haplotype frequencies and the comparisons with the previously determined Australian Caucasian and Japanese haplotypes (14). Assuming no linkage disequilibrium (random assortment of the alleles) for the three POALINs (loci), we would expect eight different haplotypes. However, only six haplotypes were observed (haplotypes A–F). The haplotype with the absence of all three elements (haplotype A) was the most common haplotype, followed by the haplotype with the presence of a single element AluyHG (haplotype D) and AluyHJ (haplotype C), having frequencies of 0.524 and 0.270, respectively. The haplotype containing all three Alu elements was not observed. A significant difference was observed for the haplotype D (only AluyHG inserted) frequencies between the Chinese and both the Japanese and Australians (P < 0.001). The frequency of haplotype A (no Alu element present) was significant (0.001 < P < 0.01) between the populations. Associations of POALINs with HLA-A and HLA-B alleles Table 3 and Table 4 show the number, percentage and delta values of HLA-A and HLA-B class I alleles associated with the POALINs. An association is not considered to be significant if only one example of an HLA allele is present in the population. Therefore, no positive associations were observed for the AluyTF element (AluyTF*2) with either the Table 2 Alu haplotypes, haplotype frequencies in the Malaysian Chinese (C) population and comparisons with the Australian (A) and Japanese (J) populations Haplotype differences between populations (P)b Haplotype frequencies (SD)a Alu haplotype Alu haplotype Id AluyHJ AluyHG AluyHF C, n ¼ 50 A, n ¼ 105 J, n ¼ 87 C–A C–J A B C D E F G 1 1 2 1 1 2 2 1 1 1 2 2 2 1 1 2 1 1 2 1 2 0.146 (0.040) 0.018 (0.018) 0.276 (0.047) 0.524 (0.055) 0.011 (0.008) 0.024 (0.012) 0.000 (0.000) 0.355 (0.035) 0.104 (0.023) 0.224 (0.030) 0.200 (0.033) 0.088 (0.023) 0.017 (0.009) 0.012 (0.010) 0.364 (0.019) 0.038 (0.016) 0.325 (0.035) 0.199 (0.028) 0.021 (0.012) 0.053 (0.019) 0.000 (0.000) 0.007 0.059 0.479 <0.001 0.065 0.767 0.436 0.006 0.513 0.549 <0.001 0.666 0.417 — SD, standard deviation. a Haplotype frequencies were determined by using the Arlequin computer software package. b Haplotype differences were calculated by the 2  2 contingency (haplotype numbers in gene pool). ª 2007 The Authors Journal compilation ª 2007 Blackwell Munksgaard  Tissue Antigens 70, 136–143 139 D. S. Dunn et al. MHC class I POALINs in a Chinese population Table 3 The number and percentage of HLA-A alleles associated with dimorphic Alu (AluyHJ, AluyHG and AluyHF) insertions in Malaysian Chinese populationa HLA-A allele Total HLA-A alleles No. with AluyHJ*2 % with AluyHJ*2 Delta No. with AluyHG*2 % with AluyHG*2 Delta No. with AluyHF*2 % with AluyHF*2 Delta HLA-A2 HLA-A11 HLA-A26 HLA-A24 HLA-A30 HLA-A33 HLA-A31 34 22 1 20 1 3 1 16 14 0 19 0 2 0 47.1 63.6 0.0 95.0 0.0 66.7 0.0 0.11 0.43 — 0.95 — 0.50 — 34 14 1 14 0 1 0 100.0 63.6 100.0 70.0 0.0 33.3 0 1.00 0.43 1.00 0.57 — 0.50b — 1 1 1 1 0 1 0 2.9 4.5 100.0 5.0 0.0 33.3 0.0 0.97b 0.95b 1.00 0.95b — 0.50b — a b Aluy*2 represents the presence of the insertion. Delta values less than 0, therefore delta# calculated. HLA-B or the HLA-A loci even though increased delta values were calculated (negative associations). The HLA-B locus expressed 18 different allelic types, but only the AluyMICB insertion and HLA-B54 (five of five) had a 100% association. The associations of the AluyMICB insertion with the other 17 HLA-B alleles were weak, moderate or indefinable. On this basis, the inferred beta block haplotypes between HLA-B and the AluyMICB added up to 22 haplotypes and are therefore not shown. In the alpha block, there were strong associations between AluyHJ*2 and HLA-A24 (95.0%), HLA-A33 (66.7%) and HLA-A11 (63.6%), but the HLA-A24 association had the largest delta value (0.95). AluyHG*2 showed a strong association with HLA-A2 (100%), HLA-A24 (70.0%) and HLA-A11 (63.6%), and the largest delta value (1.00) was obtained for the HLA-A2 association. HLA-A11 and HLA-A24 were associated with both AluyHJ and AluyHG at moderate to high levels. Inferred alpha block haplotypes between HLA-A and three POALIN loci The four-loci haplotypes in the alpha block were composed of the HLA-A locus and the three POALINs AluyHJ, AluyHG and AluyHF. Table 5 lists the haplotype identities, definition (allelic state) and frequencies of the four-loci alpha block haplotypes. The four-loci haplotypes were named by employing an alpha-numeric code; a number that refers to the HLA-A allele, followed by the same letter as for the three-loci POALIN haplotypes. More than 75% of the haplotypes (combined haplotype frequency of 0.756) in this population consisted of four distinct haplotypes with Table 4 The number and percentage of HLA-B alleles associated with the dimorphic AluyMICB and AluyTF in Malaysian Chinese populationa HLA-B allele Total HLA-B alleles No. with AluyMICB*2 % with AluyMICB*2 Delta No. with AluyTF*2 % with AluyTF*2 Delta HLA-B7 HLA-B13 HLA-B27 HLA-B35 HLA-B46 HLA-B54 HLA-B55 HLA-B61 HLA-B40/60 HLA-B75 HLA-B62 HLA-B48 HLA-B58 HLA-B38 HLA-B39 HLA-B76 HLA-B52 HLA-B51 1 5 1 5 ...
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Running head: Summary




Background information
The immune system regulation and medicine transplantation are well supported by the
human leucocyte antigen, which is available in the histocompatibility complex within the
chromosome 6 (Marsh SGE, Parham, Barber, 1999; Menier, Saez, Horejsi, 2003). The Alu
elements are contained in the human genome and are said to be the most abundant. Still, the
already inserted ones are well placed contrarily to the new generation of Alu elements that are
transplanted. Getting the newly inserted Alu elements is quite challenging within the human
genome. Across the different human populations, the distribution of Alu elements tends to vary
(Devine et al., 2004). POALINs have widely been used across various human groups to conduct
studies since they are viewed as useful genetic markers (Bamshad et al. 2001). A study by
Longman-Jacobsen et al.; (200...

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