analysis of alu repeat elements
DESCRIPTION
Analysis of Alu repeat elements. Molecular biology & Phylogeny Laboratory Woo-Yeon Kim. CONTENTS. Whole-genome analysis of Alu repeat elements reveals complex evolutionary history INTRODUCTION NEW IDEAS RESULTS DISCUSSIONS - PowerPoint PPT PresentationTRANSCRIPT
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Pusan National UniversityInterdisciplinary Research Program of Bioinformatics
IRPB
Analysis of Analysis of AluAlu repeat elements repeat elements
Molecular biology & Phylogeny Laboratory
Woo-Yeon Kim
CONTENTSCONTENTS
Whole-genome analysis of Alu repeat elements reveals complex evolutionary history INTRODUCTION NEW IDEAS RESULTS DISCUSSIONS
Alu repeat analysis in the complete human genome: trends and variations with respect to genomic composition
Genome ResearchGenome Research - Letter - Letter
Supplemental material is available online at www.genome.org
AluAlu repeats repeats
A family of SINEs, short interspersed nuclear elements Replicating via LINE-mediated reverse transcription of
an RNA polymerase Ⅲ transcript Roughly 280 bp The history of substitution patterns in the human genome Markers to determine genetic distances between human
subpopulations – polymorphic Alu insertions
RL Poly Asignal
Poly Asignal
AAAAA AAAAA SINE Structure
KK-means-means
Place K points into the space represented by the objects that are being clustered. These points represent initial group centroids.
Assign each object to the group that has the closest centroid.
When all objects have been assigned, recalculate the positions of the K centroids.
Repeat Steps 2 and 3 until the centroids no longer move. This produces a separation of the objects into groups from which the metric to be minimized can be calculated.
An example using real dataAn example using real data
Only the 5 Alu positions with diagnostic mutations in the Ya5 subfamily (position 91, 98, 146, 175, and 238)
Applying k-means clustering, k = 2
Looking for overrepresented pairsLooking for overrepresented pairs
Identifying nested subfamilies
Computing biprofiles, frequencies of pairs of nucleotide values
Aligned consensus sequences of selected subfamiliesAligned consensus sequences of selected subfamilies
Roughly 480,000 full-length Alu elements Recursively split subfamilies Identifying 213 subfamilies
DISCUSSIONDISCUSSION
Significant mutation from the consensus sequence Available detected by a rigorous whole-genome analysis Partial results
Not statistically discernible Limitations in this algorithm
Limitations – Excluding Insertion/deletion mutations Frequent CpG mutations Mutations to nucleotide values already present in other subfamilies Statistically distinguishable subfamilies
Only 19 of the 31 subfamilies currently reported in Repbase Update
BioinformaticsBioinformatics – Discovery Note – Discovery Note
Online Supplementary data is available at the web page www.igib.res.in/manuscriptdata/aluanalysis.html
AluAlu distribution in whole genome distribution in whole genome
Chromosome Alu J Alu S Alu Y Other Alus Total Alu No. Chromosome Size (bp)
1 25043 56044 12209 8114 101410 221782893
2 19679 46673 11295 6438 84085 237637456
3 15812 37539 9135 5044 67530 194846173
4 12857 30347 8158 4242 55604 188402715
5 12932 32423 8023 4351 57729 177705559
6 14449 35722 8375 4959 63505 175762617
7 17486 38816 8277 5150 69729 153794793
8 12092 27148 6203 3825 49268 142788062
9 10741 26910 6496 3441 47588 117013362
10 13909 31110 6707 4378 56104 131098977
11 11858 27461 6357 3744 49420 133239679
12 14932 32314 7026 4718 58990 129362603
13 6467 15929 4307 2114 28817 95228136
14 8921 20201 4392 2931 36445 88182284
15 9631 22169 5284 3000 40084 83582680
16 13913 29451 5462 3864 52690 80889146
17 13542 34653 7025 4150 59370 80734148
18 5935 13285 3333 1915 24468 74619305
19 14135 34297 6130 3912 58474 56446152
20 7245 16478 3058 2236 29017 59424940
21 2681 6965 1865 752 12263 33917895
22 5378 13590 3119 1586 23673 33821705
X 11160 25841 5405 3284 45690 147274156
Y 1699 3547 1128 465 6839 22660226
Un 86 226 68 39 419 1374146
1179211
Fig.1. (a) Number of Alu repeats in different chromosomes in human genome with vertical segments representing the numbers corresponding to each Alu subfamily
AluAlu repeat density and association with genes repeat density and association with genes
Fig. 1. (b) Variation in Alu and gene densities in human genome
AluAlu in intergenic and intragenic regions in intergenic and intragenic regions
Variation in Alu contents in Genes of human Genome
Alu densities in the intergenic and intragenic regions in human genome
Distribution of Distribution of AluAlu subfamilies subfamilies
The most abundant Alu subfamily – Alu S, 6.4 % region of the genome
Chromosome Y The most Alu poor chromosome High density Alu Y – very low density Alu S, Alu J
Chromosome 13, 9 – similar trend 13 having least density of Alu J
Chromosome 8, X High density Alu S, J Very low density Alu Y
Correlation analysisCorrelation analysis
GC content seems to have highest association with Alu density overall, followed by gene density and intron density
DISCUSSIONDISCUSSION
Analysis of Alu distribution in genes Statistically significant correlation between Alu and gene densities A higher Alu density in intragenic regions – These elements are
preferred in genes. The highest Alu and gene densities – Chromosome 19, 22 Alu density is correlated in the order GC content > gene density >
intron density The abundance of Alu subfamilies – Alu S > Alu J > Alu Y
Young subfamilies - Chromosome 9, 13 and Y Old subfamilies – Chromosome 8 and X Higher correlation of older Alus with GC content than younger ones