Montgomery Slatkin The American Journal of Human Genetics

Slides:

Advertisements

Similar presentations

Sampling distributions of alleles under models of neutral evolution.

Advertisements

Forward Genealogical Simulations Assumptions:1) Fixed population size 2) Fixed mating time Step #1:The mating process: For a fixed population size N, there.

Discrete Math 6-1 Copyright © Genetic Computer School 2007 Lesson 6 Probability.

Previous Estimates of Mitochondrial DNA Mutation Level Variance Did Not Account for Sampling Error: Comparing the mtDNA Genetic Bottleneck in Mice and.

Connexin Mutations in Skin Disease and Hearing Loss David P. Kelsell, Wei-Li Di, Mark J. Houseman The American Journal of Human Genetics Volume 68, Issue.

Functional Analysis of the Neurofibromatosis Type 2 Protein by Means of Disease- Causing Point Mutations Renee P. Stokowski, David R. Cox The American.

Population genetics. coalesce 1.To grow together; fuse. 2.To come together so as to form one whole; unite: The rebel units coalesced into one army to.

Gene Preference in Maple Syrup Urine Disease Mary M. Nellis, Dean J. Danner The American Journal of Human Genetics Volume 68, Issue 1, Pages (January.

Maple Syrup Urine Disease: Identification and Carrier-Frequency Determination of a Novel Founder Mutation in the Ashkenazi Jewish Population Lisa Edelmann,

Peopling of Sahul: mtDNA Variation in Aboriginal Australian and Papua New Guinean Populations Alan J. Redd, Mark Stoneking The American Journal of Human.

Polymorphism Polymorphism: when two or more alleles at a locus exist in a population at the same time. Nucleotide diversity: P = xixjpij considers.

Ancient Wolf Genome Reveals an Early Divergence of Domestic Dog Ancestors and Admixture into High-Latitude Breeds Pontus Skoglund, Erik Ersmark, Eleftheria.

Transmission/Disequilibrium Tests for Extended Marker Haplotypes

Harald H.H. Göring, Joseph D. Terwilliger

Testing the Neutral Mutation Hypothesis

Charmaine D. Royal, John Novembre, Stephanie M. Fullerton, David B

Robustness and Power of the Maximum-Likelihood–Binomial and Maximum-Likelihood– Score Methods, in Multipoint Linkage Analysis of Affected-Sibship Data

Crohn Disease: Frequency and Nature of CARD15 Mutations in Ashkenazi and Sephardi/Oriental Jewish Families Turgut Tukel, Daniel Present, Daniel Rachmilewitz,

World Kidney Day 2014: CKD and the Aging Population

Lecture 2: Basic Population Genetics

Optimized Group Sequential Study Designs for Tests of Genetic Linkage and Association in Complex Diseases Inke R. König, Helmut Schäfer, Hans-Helge Müller,

Volume 21, Issue 20, Pages R837-R838 (October 2011)

CHEK2*1100delC and Susceptibility to Breast Cancer: A Collaborative Analysis Involving 10,860 Breast Cancer Cases and 9,065 Controls from 10 Studies

Montgomery Slatkin The American Journal of Human Genetics

Caroline Durrant, Krina T. Zondervan, Lon R

David H. Spencer, Kerry L. Bubb, Maynard V. Olson

Tuuli Lappalainen, Stephen B. Montgomery, Alexandra C

Coupling Genetic and Ecological-Niche Models to Examine How Past Population Distributions Contribute to Divergence L. Lacey Knowles, Bryan C. Carstens,

A Predominantly Indigenous Paternal Heritage for the Austronesian-Speaking Peoples of Insular Southeast Asia and Oceania Cristian Capelli, James F. Wilson,

Biased Gene Conversion Skews Allele Frequencies in Human Populations, Increasing the Disease Burden of Recessive Alleles Joseph Lachance, Sarah A. Tishkoff

Agnar Helgason, Sigrún Sigurðardóttir, Jeffrey R

John Wakeley, Rasmus Nielsen, Shau Neen Liu-Cordero, Kristin Ardlie

XMCPDT Does Have Correct Type I Error Rates

The Future of Association Studies: Gene-Based Analysis and Replication

Maternal History of Oceania from Complete mtDNA Genomes: Contrasting Ancient Diversity with Recent Homogenization Due to the Austronesian Expansion Ana T.

Lower-Than-Expected Linkage Disequilibrium between Tightly Linked Markers in Humans Suggests a Role for Gene Conversion Kristin Ardlie, Shau Neen Liu-Cordero,

A Flexible Bayesian Framework for Modeling Haplotype Association with Disease, Allowing for Dominance Effects of the Underlying Causative Variants Andrew.

Haplotype Fine Mapping by Evolutionary Trees

An African American Paternal Lineage Adds an Extremely Ancient Root to the Human Y Chromosome Phylogenetic Tree Fernando L. Mendez, Thomas Krahn, Bonnie.

Characteristics of Neutral and Deleterious Protein-Coding Variation among Individuals and Populations Wenqing Fu, Rachel M. Gittelman, Michael J. Bamshad,

Are Rare Variants Responsible for Susceptibility to Complex Diseases?

George A. Diaz, Bruce D. Gelb, Neil Risch, Torbjoern G

Christoph Lange, Nan M. Laird The American Journal of Human Genetics

Jon Wakefield The American Journal of Human Genetics

Pier Francesco Palamara, Laurent C. Francioli, Peter R

Hal M. Hoffman, Fred A. Wright, David H. Broide, Alan A

No Gene Is an Island: The Flip-Flop Phenomenon

Shuhua Xu, Wei Huang, Ji Qian, Li Jin

Erratum The American Journal of Human Genetics

Molecular Analysis of the β-Globin Gene Cluster in the Niokholo Mandenka Population Reveals a Recent Origin of the βS Senegal Mutation Mathias Currat,

Historical Biogeography: The New Synthesis

Daniel J. Schaid, Shannon K. McDonnell, Scott J. Hebbring, Julie M

Whole-Genome-Sequence-Based Haplotypes Reveal Single Origin of the Sickle Allele during the Holocene Wet Phase Daniel Shriner, Charles N. Rotimi The.

Benjamin A. Rybicki, Robert C. Elston

A Unified Approach to Genotype Imputation and Haplotype-Phase Inference for Large Data Sets of Trios and Unrelated Individuals Brian L. Browning, Sharon.

Gad Kimmel, Ron Shamir The American Journal of Human Genetics

Population Structure in Admixed Populations: Effect of Admixture Dynamics on the Pattern of Linkage Disequilibrium C.L. Pfaff, E.J. Parra, C. Bonilla,

Increasing the Power and Efficiency of Disease-Marker Case-Control Association Studies through Use of Allele-Sharing Information Tasha E. Fingerlin,

Phylogenetic and Familial Estimates of Mitochondrial Substitution Rates: Study of Control Region Mutations in Deep-Rooting Pedigrees Evelyne Heyer, Ewa.

Powerful Multilocus Tests of Genetic Association in the Presence of Gene-Gene and Gene-Environment Interactions Nilanjan Chatterjee, Zeynep Kalaylioglu,

Test for Interaction between Two Unlinked Loci

Yu Zhang, Tianhua Niu, Jun S. Liu

Ancient Wolf Genome Reveals an Early Divergence of Domestic Dog Ancestors and Admixture into High-Latitude Breeds Pontus Skoglund, Erik Ersmark, Eleftheria.

Iuliana Ionita-Laza, Seunggeun Lee, Vlad Makarov, Joseph D

Alice S. Whittemore, Jerry Halpern

Genetic Anthropology of the Colorectal Cancer–Susceptibility Allele APC I1307K: Evidence of Genetic Drift within the Ashkenazim Bethany L. Niell, Jeffrey.

Messages through Bottlenecks: On the Combined Use of Slow and Fast Evolving Polymorphic Markers on the Human Y Chromosome Peter de Knijff The American.

Passorn Wonnapinij, Patrick F. Chinnery, David C. Samuels

Bruce Rannala, Jeff P. Reeve The American Journal of Human Genetics

The Size Distribution of Homozygous Segments in the Human Genome

Presentation transcript:

A Population-Genetic Test of Founder Effects and Implications for Ashkenazi Jewish Diseases Montgomery Slatkin The American Journal of Human Genetics Volume 75, Issue 2, Pages 282-293 (August 2004) DOI: 10.1086/423146 Copyright © 2004 The American Society of Human Genetics Terms and Conditions

Figure 1 Illustration of an intra-allelic genealogy for the case with i=4. t1 is the age of the allele A, t2 is the time of the most recent common ancestor (MRCA) of copies of A in the sample, and w is the length of branch on which A arose by mutation. The American Journal of Human Genetics 2004 75, 282-293DOI: (10.1086/423146) Copyright © 2004 The American Society of Human Genetics Terms and Conditions

Figure 2 Estimated posterior probability distributions of the number of ancestral lineages, m, carrying N370S at GBA (which causes Gaucher disease) for the nine combinations of N0 (the population size at a.d. 70) and N1 (the population size at a.d. 1348) and two different hypothesized times of founder events (a.d. 75 and 1350). The American Journal of Human Genetics 2004 75, 282-293DOI: (10.1086/423146) Copyright © 2004 The American Society of Human Genetics Terms and Conditions

Figure 3 Scatterplot of t2 (the coalescence time of all copies of A) and jo (the number of nonrecombinants) generated in 1,000 replicate forward simulations of a neutral allele that was in one copy t1 generations in the past and was found at t=0 with a frequency between 0.027 and 0.037 (i.e., x=0.032±0.005, which was chosen to match the frequency of N370S at GBA, 0.032). In each replicate, the allele age (t1) was chosen randomly from a probability distribution on t in which Pr(t) is proportional to n(t), where n(t) is based on table 1 with n0=600 and n1=3,000. Parameters for A and the linked marker are the same as for N370S at GBA: i=268, jo=163, pN=0.205, and θ=0.007 (cf. table 2). The American Journal of Human Genetics 2004 75, 282-293DOI: (10.1086/423146) Copyright © 2004 The American Society of Human Genetics Terms and Conditions

Figure 4 The probability that an allele present in one copy at t=0 is still segregating and has a frequency of at least x 26.08 generations later. Calculations were made using the theory described in the appendix. The American Journal of Human Genetics 2004 75, 282-293DOI: (10.1086/423146) Copyright © 2004 The American Society of Human Genetics Terms and Conditions