Download Alu

IRPB
Analysis of Alu repeat elements
Pusan National University
Interdisciplinary Research Program of Bioinformatics
Molecular biology & Phylogeny Laboratory
Woo-Yeon Kim
[email protected]
1
CONTENTS

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
[email protected]
2
Genome Research - Letter
Supplemental material is available online at www.genome.org
[email protected]
3
INTRODUCTION
[email protected]
4
Alu 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
L
Poly A
signal
AAAAA
R
Poly A
signal
AAAAA
SINE Structure
[email protected]
5
K-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.
[email protected]
6
NEW IDEAS
[email protected]
7
An 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
[email protected]
8
Looking for overrepresented pairs


Identifying nested
subfamilies
Computing biprofiles,
frequencies of pairs of
nucleotide values
[email protected]
9
RESULTS
[email protected]
10
Aligned consensus sequences of selected subfamilies

Roughly 480,000 full-length Alu elements
 Recursively split subfamilies
 Identifying 213 subfamilies
[email protected]
11
An evolutionary tree of Alu subfamilies
[email protected]
12
DISCUSSION

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
[email protected]
13
Bioinformatics – Discovery Note
Online Supplementary data is available at the web page
www.igib.res.in/manuscriptdata/aluanalysis.html
[email protected]
14
Alu 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
Fig.1. (a) Number of Alu repeats in different chromosomes in human genome
with vertical segments representing the numbers corresponding to each Alu
subfamily
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
[email protected]
1179211
15
Alu repeat density and association with genes
Fig. 1. (b) Variation in Alu and gene densities in human genome
[email protected]
16
Alu 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
[email protected]
17
Distribution of Alu 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
[email protected]
18
Correlation analysis
GC content seems to have highest association with Alu density
overall, followed by gene density and intron density
[email protected]
19
DISCUSSION

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
[email protected]
20