Using Familias and FamLink Athens 29 May, 2014

Familias 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

Familias 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES – Calculate likelihoods in relationship testing – Define “arbitrary” relationships – Different mutation models – Silent alleles – Subpopulation correction – Generate pedigrees – Calculate priors – Easy to use / Userfriendly

Familias – At a glance 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Define general frequency database -Change mutations

Familias – At a glance 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Define marker specific database sizes -Define dropout probability -Mutations -Silent allele

Familias – At a glance 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Case data dialog -Import/Edit DNA data -Compare profiles

Familias – At a glance 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Compare profiles

Familias – At a glance 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Random match probability

Familias – At a glance 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Define pedigrees/hypotheses

Familias – At a glance 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Defining relations -As Parent-Child Paternity: Siblings: ParentChild Alleged fatherChild MotherChild ParentChild FatherSibling1 MotherSibling1 FatherSibling2 MotherSibling2

Recent news in Familias 3 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES – New mutation model – Simulation interface – DVI module – Blind search feature – Direct matching – Random match calculation – Create database feature – Dropouts

Familias – Simulations 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Simulation options

Familias – Simulations 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Simulation results

Familias – Simulations 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Simulations -Find good thresholds -False positive/negative rate -Investigate what we can expect -Include -Kinship -Mutations -Silent alleles -Multiple pedigrees -Investigate the number of persons we must genotype -Investigate the number of markers we must include

Familias – DVI 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -What is a DVI operation? -What is the purpose of developing a DVI module? -“Alternative” softwares -Brief overview -Blind search module

Familias – DVI 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Add Unidentified persons

Familias – DVI 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Blind search

Familias – DVI 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Blind search results

Familias – DVI 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Add reference data

Familias – DVI 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Edit reference family

Familias – DVI 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -Matching

Familias – Dropouts 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES -What is a dropout? -The model -Conditional genotype probabilities -Dropout probability -Low quality profiles -Estimation of dropout probabilities -Logistic regression -LR for a number of dropout probabilities

Dropout versus silent allele 23 L1: 16,17 L2: 10,11 L1: 17,18 L2: 10,10 L1: 19,19 L2: 12,12

Familias–Questions? 30 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink  What can FamLink do? –––––– User-friendly software Similar to Familias in many ways Perform likelihood calculations on a number of pedigrees Takes linkage between markers into account Does not implement a good mutation model Simulation interface predefined –––––––– Implements the Lander-Green Different than Familias Merlin algorithm 10 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink – At a glance –Defineallelefrequencydatabase –Currently restricted to two markers 11 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink – At a glance –Definerecombinationrate –Between 0 and w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink – At a glance –Convertgeneticdistance(cM)(cM)torecombinationrate 13 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink – At a glance –Selectmainhypothesis 14 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink – At a glance –Selectalternativehypotheses 15 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink – At a glance –DefineDNADNAdata 16 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink – At a glance –Calculatelikelihoods –We display two methods 17 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink – Familias connection –Calculate likelihoods for aFamiliasproject –Get likelihoods for all your markers LinkageLinkageconsideredfor all markers 18 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

FamLink–Questions? 30 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES

EXERCISES 31 w w.umb.no NORWEGIAN UNIVERSITY OF LIFE SCIENCES