UPDtool:

a tool for detection of iso- and

heterodisomy in

parent–child trios using SNP

microarrays presented by Sarah Azadmehr

BIOINFORMATICS 2013

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Introduction

• Uniparental Disomy

• Gold Standard

Microsatellite array

Trio SNP microarrays

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(Mendelian Errors)MEs

• Non-Mendelian errors/genotyping errors

• low rate, <1%

• Mendel's laws

• Segregation

• Independent assortment

• Dominance Extranuclear inheritance,genomic imprinting,Mosaicism,De novo

Mutations,3nt repeats disorders,UPD

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What is imprinting?

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UPD

• Rare phenomenon 1/3,500

• As a Mendelian error

• malsegregation in meiotic or mitotic

divisions or cross overs

• Inheritance from one parent

Paternal/Maternal origination

• homologues or sister chromatids Mixture

heterodisomy or isodisomy

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UPD

• whole chromosome / a segment

• No harmful ostentation Unless

imprinted genes or homozygosity in AR

• survivor in trisomy and monosomy

corrections Silver–Russell syndrome (chr.7, maternal)

Prader–Willi syndrome (chr. 15, maternal)

1988 CF(chr.7,maternal)

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Title

• Text

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Microsatellite analysis

• laborious, expensive

• limited number of markers

• Limited informative value in

consanguineous families

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SNP microarrays

• SNPs occur every 300-1000bp

provide hundreds of thousands of genotypes

• Most of them have no effect

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METHOD AND RESULTS

• 5 positive -30 negative samples

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Suppl. Figure 1: Results for chromosome 7 of patient 1

Maternal isodisomy

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Suppl. Figure 2: Results for chromosome 7 of patient 2

Maternal isodisomy

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Suppl. Figure 3: Results for chromosome 9 of patient 3

Paternal isodisomy

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Suppl. Figure 4: Results for chromosome 14 of patient 4

From ~ 20 MB to ~ 90 MB maternal heterodisomy.

From ~ 95 MB to the end of the chromosome maternal isodisomy

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Suppl. Figure 5: Results for chromosome 14 of patient 5

2 maternal heterodisomic regions (~20 MB to 25 MB, ~ 73 MB to the end of the chromosome)

A maternal isodisomic stretch in between both heterodisomic regions

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CONCLUSION

• Fast algorithm detection of hetero- and

isodisomies from maternal and paternal

• The breakpoints between hetero- and

isodisomy determintion more precisely

than by microsatellite analysis

• confirm the rate of MEs

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Thanks for your

attention!

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