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

Slides:

Advertisements

Similar presentations

Novel PMS2 Pseudogenes Can Conceal Recessive Mutations Causing a Distinctive Childhood Cancer Syndrome Michel De Vos, Bruce E. Hayward, Susan Picton, Eamonn.

Advertisements

Nuclear and Mitochondrial DNA Analysis of a 2,000-Year-Old Necropolis in the Egyin Gol Valley of Mongolia Christine Keyser-Tracqui, Eric Crubézy, Bertrand.

Length Distributions of Identity by Descent Reveal Fine-Scale Demographic History Pier Francesco Palamara, Todd Lencz, Ariel Darvasi, Itsik Pe’er The American.

TFIIH Subunit Alterations Causing Xeroderma Pigmentosum and Trichothiodystrophy Specifically Disturb Several Steps during Transcription Amita Singh, Emanuel.

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

Math b (Discrete) Random Variables, Binomial Distribution.

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.

Differential Relationship of DNA Replication Timing to Different Forms of Human Mutation and Variation Amnon Koren, Paz Polak, James Nemesh, Jacob J. Michaelson,

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

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.

Copyright © 2010 Pearson Addison-Wesley. All rights reserved. Chapter 3 Random Variables and Probability Distributions.

Alternative Splicing QTLs in European and African Populations Halit Ongen, Emmanouil T. Dermitzakis The American Journal of Human Genetics Volume 97, Issue.

A Multilocus Model of the Genetic Architecture of Autoimmune Thyroid Disorder, with Clinical Implications Veronica J. Vieland, Yungui Huang, Christopher.

Mutations in LARS2, Encoding Mitochondrial Leucyl-tRNA Synthetase, Lead to Premature Ovarian Failure and Hearing Loss in Perrault Syndrome Sarah B. Pierce,

Genomewide Comparison of DNA Sequences between Humans and Chimpanzees Ingo Ebersberger, Dirk Metzler, Carsten Schwarz, Svante Pääbo The American Journal.

Fragile X and X-Linked Intellectual Disability: Four Decades of Discovery Herbert A. Lubs, Roger E. Stevenson, Charles E. Schwartz The American Journal.

Copyright © 2010 Pearson Addison-Wesley. All rights reserved. Chapter 3 Random Variables and Probability Distributions.

PRIMUS: Rapid Reconstruction of Pedigrees from Genome-wide Estimates of Identity by Descent Jeffrey Staples, Dandi Qiao, Michael H. Cho, Edwin K. Silverman,

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

Montgomery Slatkin The American Journal of Human Genetics

Genetic Landscape of Eurasia and “Admixture” in Uyghurs

Public Opinion about the Importance of Privacy in Biobank Research

Jacek Majewski The American Journal of Human Genetics

P. Y. W. Man, P. G. Griffiths, D. T. Brown, N. Howell, D. M

2016 Curt Stern Award Address: From Rare to Common Diseases: Translating Genetic Discovery to Therapy1 Brendan Lee The American Journal of Human Genetics

The Structure of Diversity within New World Mitochondrial DNA Haplogroups: Implications for the Prehistory of North America Ripan S. Malhi, Jason A.

Somatic Mutations throughout the Entire Mitochondrial Genome Are Associated with Elevated PSA Levels in Prostate Cancer Patients Anita Kloss-Brandstätter,

Montgomery Slatkin The American Journal of Human Genetics

Genetics, Individuality, and Medicine in the 21st Century*

XMCPDT Does Have Correct Type I Error Rates

Xiangqing Sun, Robert Elston, Nathan Morris, Xiaofeng Zhu

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

Random-Effects Model Aimed at Discovering Associations in Meta-Analysis of Genome- wide Association Studies Buhm Han, Eleazar Eskin The American Journal.

Probability Distribution.

Family-Based Association Studies for Next-Generation Sequencing

Sang Hong Lee, Naomi R. Wray, Michael E. Goddard, Peter M. Visscher

Alkes L. Price, Gregory V. Kryukov, Paul I. W. de Bakker, Shaun M

Are Rare Variants Responsible for Susceptibility to Complex Diseases?

Rapid and Sensitive Real-Time Polymerase Chain Reaction Method for Detection and Quantification of 3243A>G Mitochondrial Point Mutation Rinki Singh,

Olga A. Derbeneva, Elena B. Starikovskaya, Douglas C. Wallace, Rem I

E. Warwick Daw, Simon C. Heath, Ellen M. Wijsman

Limited Clinical Utility of Non-invasive Prenatal Testing for Subchromosomal Abnormalities Kitty K. Lo, Evangelia Karampetsou, Christopher Boustred,

The SNP Endgame: A Multidisciplinary Approach*

Family-Based Tests of Association in the Presence of Linkage

Erratum The American Journal of Human Genetics

Estimating Genetic Effects and Quantifying Missing Heritability Explained by Identified Rare-Variant Associations Dajiang J. Liu, Suzanne M. Leal The.

Genetically Determined Partial Complement C4 Deficiency States Are Not Independent Risk Factors for SLE in UK and Spanish Populations Lora Boteva, David L.

J.L. Elson, D.C. Samuels, D.M. Turnbull, P.F. Chinnery

Wei Pan, Il-Youp Kwak, Peng Wei The American Journal of Human Genetics

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

Statistical Treatment of Fluorescence in Situ Hybridization Validation Data to Generate Normal Reference Ranges Using Excel Functions Allison L. Ciolino,

Probability Distribution.

L-GATOR: Genetic Association Testing for a Longitudinally Measured Quantitative Trait in Samples with Related Individuals Xiaowei Wu, Mary Sara McPeek

Jung-Ying Tzeng, Chih-Hao Wang, Jau-Tsuen Kao, Chuhsing Kate Hsiao

BRCA1 and BRCA2 Testing: Weighing the Demand against the Benefits

Efficient Computation of Significance Levels for Multiple Associations in Large Studies of Correlated Data, Including Genomewide Association Studies

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

The Frequency of Heteroplasmy in the HVII Region of mtDNA Differs across Tissue Types and Increases with Age Cassandra D. Calloway, Rebecca L. Reynolds,

Hereditary mtDNA Heteroplasmy: A Baseline for Aging?

On the Etruscan Mitochondrial DNA Contribution to Modern Humans

Alice S. Whittemore, Jerry Halpern

A Highly Unstable Recent Mutation in Human mtDNA

Hannah R. Elliott, David C. Samuels, James A. Eden, Caroline L

Zuoheng Wang, Mary Sara McPeek The American Journal of Human Genetics

Matching Mitochondrial DNA Haplotypes for Circumventing Tissue-Specific Segregation Bias Jianxin Pan, Li Wang, Charles Lu, Yanming Zhu, Zhunyuan Min,

Examining Variation in Recombination Levels in the Human Female: A Test of the Production-Line Hypothesis Ross Rowsey, Jennifer Gruhn, Karl W. Broman,

Genomewide Comparison of DNA Sequences between Humans and Chimpanzees

Iain G. Johnston, Nick S. Jones The American Journal of Human Genetics

Mitochondrial DNA as a Cancer Biomarker

The Size Distribution of Homozygous Segments in the Human Genome

Presentation transcript:

The Distribution of Mitochondrial DNA Heteroplasmy Due to Random Genetic Drift Passorn Wonnapinij, Patrick F. Chinnery, David C. Samuels The American Journal of Human Genetics Volume 83, Issue 5, Pages 582-593 (November 2008) DOI: 10.1016/j.ajhg.2008.10.007 Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 1 The Heteroplasmy Distribution of the A3243G mtDNA Mutation in a Sample of Human Primary Oocytes Is Compared to the Kimura Distribution (A) Frequency histogram of the heteroplasmy in both the data and the Kimura distribution fit to the data. Parameter values for the Kimura distribution are given in Table 1 for all figures. (B) Cumulative probability distribution functions for the data and the Kimura distribution fit to the data. A KS test indicates that there is no significant difference between the measured and the theoretical probability distributions. The American Journal of Human Genetics 2008 83, 582-593DOI: (10.1016/j.ajhg.2008.10.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 2 The Measured Heteroplasmy Distribution from Offspring and Mature Oocytes in the Heteroplasmic Mouse Line 515 Is Compared to the Kimura Distribution (A) The heteroplasmy frequency histogram from the offspring. (B) KS test comparing the offspring heteroplasmy data to the Kimura distribution fit to the data. (C) The heteroplasmy frequency histogram of the mature oocytes in the 515 line. (D) KS test for the line 515 mature oocyte data. There is a significant difference between the two distributions in the mature oocyte data. The American Journal of Human Genetics 2008 83, 582-593DOI: (10.1016/j.ajhg.2008.10.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 3 The Measured Heteroplasmy Distribution from Offspring and Mature Oocytes in the Heteroplasmic Mouse Line 517 Is Compared to the Kimura Distribution (A) The heteroplasmy frequency histogram from the offspring. (B) KS test comparing the offspring heteroplasmy data to the Kimura distribution fit to the data. (C) The heteroplasmy frequency histogram of the mature oocytes in the 517 line. (D) KS test for the data from line 517 mature oocytes. The American Journal of Human Genetics 2008 83, 582-593DOI: (10.1016/j.ajhg.2008.10.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 4 The Measured Heteroplasmy Distribution from Mature Oocytes and Primary Oocytes in the Heteroplasmic Mouse Line 603A Is Compared to the Kimura Distribution (A) The heteroplasmy frequency histogram of the mature oocytes in the 603A line. (B) KS test for the data from line 603A mature oocytes. (C) The heteroplasmy frequency histogram of the primary oocytes in the 603A line. (D) KS test for the data from line 603A primary oocytes. There is a significant difference between the two distributions for the primary oocyte data. The American Journal of Human Genetics 2008 83, 582-593DOI: (10.1016/j.ajhg.2008.10.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 5 The Measured Heteroplasmy Distribution from Mature Oocytes and Primary Oocytes in the Heteroplasmic Mouse Line 603B Is Compared to the Kimura Distribution (A) The heteroplasmy frequency histogram of the mature oocytes in the 603B line. (B) KS test for the data from line 603B mature oocytes. (C) The heteroplasmy frequency histogram of the primary oocytes in the 603B line. (D) KS test for the data from line 603B primary oocytes. The American Journal of Human Genetics 2008 83, 582-593DOI: (10.1016/j.ajhg.2008.10.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 6 The Measured Heteroplasmy Distribution from Unfertilized Eggs in the Heteroplasmic Drosophila mauritiana Lines H1, G20-5, and G71-12 Is Compared to the Kimura Distribution (A) The heteroplasmy frequency histogram of the Drosophila line H1 and the Kimura distribution fit to the mean and variance values from these data. (B) The KS test comparing the data with the Kimura distribution. There is a significant difference between the two distributions for line H1. (C) The heteroplasmy frequency histogram for the Drosophila line G20-5 is compared to the Kimura distribution. (D) KS test comparing the data for Drosophila line G20-5 to the Kimura distribution. (E) The heteroplasmy frequency histogram from the Drosophila line G71-12 is compared to the Kimura distribution. (F) KS test comparing the data for Drosophila line G71-12 to the Kimura distribution. The American Journal of Human Genetics 2008 83, 582-593DOI: (10.1016/j.ajhg.2008.10.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 7 The Measured Heteroplasmy Distribution from Unfertilized Eggs in the Heteroplasmic Drosophila mauritiana Lines H1-31M, H1-18D, and H1-12B Is Compared to the Kimura Distribution (A) The heteroplasmy frequency histogram from the Drosophila line H1-31M and the Kimura distribution. (B) The KS test comparing the heteroplasmy data for Drosophila line H1-31M to the Kimura distribution. (C) The heteroplasmy frequency histogram from the Drosophila line H1-18D is compared to the Kimura distribution. (D) KS test comparing the Drosophila line H1-18D to the Kimura distribution. (E) The heteroplasmy frequency histogram from Drosophila line H1-12B is compared to the Kimura distribution. (F) KS test comparing data for Drosophila line H1-12B and the Kimura distribution. The American Journal of Human Genetics 2008 83, 582-593DOI: (10.1016/j.ajhg.2008.10.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 8 Comparison of Measured Heteroplasmy Distribution from Drosophila simulans Unfertilized Eggs with the Kimura Distribution (A) Heteroplasmy frequency histogram and the Kimura distribution fit to these data. (B) KS test comparing the data to the Kimura distribution. The American Journal of Human Genetics 2008 83, 582-593DOI: (10.1016/j.ajhg.2008.10.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 9 Comparison of a Kimura Distribution, Normal Distribution, and Binomial Distribution with Mean = 0.1 and Variance = 0.01 (A) Kimura distribution. The probability density ϕ(x) is plotted. (B) Normal distribution. (C) Binomial distribution. The mean and variance values require a range of discrete states from zero to nine, giving discrete probability values of 0, 1/9, 2/9, etc. The American Journal of Human Genetics 2008 83, 582-593DOI: (10.1016/j.ajhg.2008.10.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions