We are a mathematical, theoretical, and computational lab in genetics
and evolution. Research in the lab addresses problems in evolutionary
biology and human genetics through a combination of mathematical
modeling, computer simulations, development of statistical methods, and
inference from population-genetic data.
describes a unifying principle that underlies the production
of anomalous gene trees (AGTs), gene trees that are more probable
under an evolutionary model than the gene tree that matches the species tree.
The new principle, identifying pairs of consecutive short branches as key to AGT
production, refines earlier work from the lab on AGTs (refs.
11-18-2013 We welcome postdoc Filippo Disanto!
Filippo joins us from the University of Cologne, where he completed an
earlier postdoctoral fellowship in population genetics and bioinformatics.
11-8-2013 A report by Doc Edge et al.
in Evolution, Medicine, and Public Health, on surprises that
occur in the application of population-genetic principles to
association mapping. The article describes windfalls arising from
population geneticsand pitfalls.
in Genetics reports an algorithm for optimizing the choice of
samples to include in sequencing studies, when the goal is accurate
genotype imputation. The algorithm is based on "phylogenetic diversity,"
the extent to which a subset of lineages captures the genealogical
structure underlying an evolutionary tree. The work extends a line of
investigation in the lab on genotype imputation
9-29-2013 We welcome several new members!
9-5-2013 We report
in Genetics in Medicine on strategies for improving the
identification of recent parental relatedness as an incidental outcome in
samples sent for clinical genomic testing. The comment highlights several
principles for detection of runs of homozygosity that we previously
reported in the work
Pemberton et al.
This month we say goodbye to Postdoc Lars Andersen. Lars's work in
the lab has focused on coalescent theory, migration models, and
Markov chains in population genetics. Lars returns to the
Department of Mathematics at the University of Aarhus, where he will
be starting a faculty position. We wish Lars all the best in his
- Bridget Algee-Hewitt; Bridget joins us as a postdoc from the
University of Tennessee, where she completed an earlier postdoctoral
fellowship in forensic anthropology.
- Arbel Harpak; Arbel joins us as a PhD student after having
completed his MS in ecology, evolution, and behavior at the
Hebrew University of Jerusalem.
- Jonathan Kang; Jonathan joins us a PhD student. His
undergraduate degree is in applied mathematics and biology from Brown
University, and most recently he has been performing research at the
Bioinformatics Institute of Singapore.
- Rohan Mehta; Rohan joins us as a PhD student after having
completed his BS in biology and mathematics at the University of
California, San Diego.
7-21-2013 PhD graduate Lucy Huang and former
postdoc Erkan Buzbas
study of a
population-genetic model of genotype imputation. The model
of Ethan Jewett et al., focusing on the role of
mutation rather than sample size. Both models provide insight into the
contribution of population-genetic parameters to the performance of
genotype imputation methods for disease association studies.
A paper by recent
Ph.D. graduate Zach Szpiech
contributes to the ongoing discussion on the population genetics of
deleterious variation in humans. Zach finds that long runs of
homozygosity (ROH) have a high level of recessive deleterious variation,
reflecting a cumulative effect of recent parental relatedness in
elevating the frequency of deleterious homozygotes. Former
Pemberton is also a contributor to the work.
5-28-2013 A comprehensive dataset on worldwide human
microsatellite variation is reported in a
new paper in G3:
Genes, Genomes, Genetics. Former
Pemberton and PhD
DeGiorgio have assembled eight major datasets, producing a
collection of >5000 individuals from >250 populations, and using the
collection to identify new features of human population structure. The
for future studies of human genetic variation.
5-21-2013 A new paper in IEEE/ACM Transactions on
Computational Biology and Bioinformatics by former
Than reports on mathematical properties of the deep coalescence
cost, a quantity useful in inferring species trees from gene trees.
Cuong's work explains an observation that deep coalescence algorithms
tend to produce estimated trees with a high degree of balance. The
paper builds upon Cuong's earlier work on deep
3-15-2013 Lab alumnus
Jakobsson has been awarded the 2013
Erlanders Prize for Science and Technology in the field of biology.
The prize, awarded every five years by the Royal Swedish Academy of
Sciences to a young investigator in Sweden, recognizes Mattias's
contributions to large-scale genetic studies of human demographic history.
Congrats to Mattias!
Generation to Generation: Scientific and Cultural Approaches to Jewish
Genetics, a course held in the autumn quarter of 2012, is profiled
2-8-2013 In this month's issue of Genetics,
Jakobsson and PhD student Doc Edge report the exact
constraint on the FST measure of population
structure at a locus as a function of the frequency of the locus's
most frequent allele. The result can be used to explain comparatively
low values of FST in diverse African human
populations and lower values of FST for rare
variants than for common variants. The work builds upon related
studies reported by the lab
The cover image illustrates the work.
Read the article.
issue highlights note]
commentary by F Rousset]
1-19-2013 In a new
reported in Molecular Biology and Evolution, recent
DeGiorgio seeks to explain why it is possible under a range
expansion for the first principal component of genetic variation to
be either parallel or perpendicular to the direction of
the expansion. The explanation involves the connection between
coalescence times, Fst, and principal components.
1-14-2013 Noah takes on the role of Editor-in-Chief
of Theoretical Population Biology! Read
the welcome editorial.
12-11-2012 The second installment of the coalescent
theory of ranked gene trees has appeared, in a paper jointly written
with former postdoc
and Tanja Stadler
(IEEE/ACM Trans Comp Biol Bioinformat 9: 1558-1568). The paper
proves a surprising result, that most species trees have a ranking that
gives rise to anomalous ranked gene trees. The paper extends
earlier work from the
lab on unranked gene trees.
Pemberton is leaving the lab to begin work as Assistant
Professor of Biochemistry and Medical Genetics at the University of
Manitoba. We wish Trevor success in his new position!
10-27-2012 In a letter to the editor of Molecular
Evolution, Erkan Buzbas
comments that an approximate Bayesian computation (ABC) method
proposed by Fan and Kubatko for species tree inference is not
technically an ABC method. While Erkan does not claim that the
method does not work well in practice, he finds that it fails to be
a proper ABC method for quite interesting reasons.
Read Erkan's ABC
10-22-2012 A new
from the lab, by Naama Kopelman et al., reports on the
behavior of admixed populations in the neighbor-joining algorithm for
constructing evolutionary trees. The theory provides explanations for a
variety of patterns seen in actual neighbor-joining trees involving
admixed populations. The paper will be presented at
on Phylogenomics and Population Genomics at the Pacific Symposium on
In a new paper,
Wang and collaborator Kari Schroeder report a new method for
estimating allelic dropout rates in microsatellite data. The method is
novel in that it is designed explicitly for the case in which no
replicate genotypes are available. Chaolong has
written MicroDrop, a program
that implements the new approach.
9-19-2012 This month, we welcome new members:
- Lars Andersen; Lars joins us as a postdoc from the University
of Aarhus, where he received his PhD in probability theory and
performed postdoctoral work in population genetics.
- Doc Edge; Doc returns as a PhD student to Stanford, where he previously completed
his BA in human biology. He joins us after earning his MA in
statistics at the University of California at Berkeley.
- Amy Goldberg; Amy rejoins us as a PhD student.
She was previously at the University of Michigan, where she completed
her BS in biological anthropology and mathematics and was an
undergraduate in the lab in its former home.
We say goodbye to:
- Erkan Buzbas, completing his postdoc and joining the faculty of the
University of Idaho as Assistant Professor of Statistical Science
- Zach Szpiech, receiving his PhD and starting a postdoc with Ryan
Hernandez, Department of Bioengineering and Therapeutic Sciences, University of
California, San Francisco
- Cuong Than, continuing in his postdoctoral studies with Daniel Huson,
Faculty of Computer Science, University of Tubingen
- Paul Verdu, completing his postdoc and joining the faculty of the
Natural History Museum of Paris as CNRS Associate Scientist
- Chaolong Wang, receiving his PhD and starting a postdoc with Liming
Liang and Xihong Lin, Department of Biostatistics, Harvard School of
We wish everyone all the best in their new positions!
8-24-2012 In a paper
Wang reports on the pattern of similarity between genes and
geography in human populations. His work standardizes analyses of
genes and geography across different data sets from geographic
regions, producing visualizations of the agreement between genetic
variation and geographic maps of population sampling locations.
Interestingly, the similarity between genes and geography is greater
in Asia, rather than in Europe, where a similarity between genes and
geography has been more widely
Editor's Choice note]
8-17-2012 A new paper
Pemberton et al. in the American Journal of
Physical Anthropology examines patterns of variation in a
distinctive endogamous group consisting of of six Gujarati villages.
Trevor finds a genetic signature of the patrilocal practice in which
marriages occur between villages, with wives moving to the husband's
8-14-2012 The lab reports on the worldwide
distribution of runs of homozygosity (ROH) in the human genome in a
recent paper by Trevor
Pemberton et al. in the American Journal of Human
Genetics. Trevor's paper also provides a new approach to
categorizing ROH by the processes that have likely generated them, and
reveals a variety of interesting geographic patterns in ROH lengths and
8-10-2012 Graduate students
Zach Szpiech and
Wang have successfully defended their PhD dissertations in
Chaolong, Noah, and Zach at the University of Michigan Department of
Computational Medicine and Biology, with graduate program director Margit
Burmeister and founding center director Gil Omenn
Zach's thesis on "Human migration, population divergence, and the
accumulation of deleterious alleles: insights from private genetic
variation and whole-exome sequencing" considers several perspectives on
private alleles, including a model of microsatellite private alleles, a
method for counting private alleles in uneven samples, and a study of
connections among rare, private, and deleterious variants.
Chaolong's thesis on "Statistical methods for analyzing human genetic
variation in diverse populations" considers new approaches for studying
spatial population-genetic variation, and develops a new method for
circumventing allelic dropout in microsatellite data without requiring
8-9-2012 A paper by Ethan Jewett et
al. describes a population-genetic model for genotype imputation.
links the framework of the coalescent to an important topic in the
implementation of genome-wide association studies, producing new
results that can help guide association study design.
6-15-2012 Two recent papers from the lab develop
improved methods for estimating species trees from gene trees. In the
first paper in the
series, Ethan Jewett has developed iGLASS,
which improves upon the method known
second paper, Laura
Helmkamp and Ethan Jewett have developed three more methods in
the same family of approaches: iSD, iSTEAC,
and iMAC. Laura and Ethan's paper appears in a special issue of
the Journal of Computational Biology in honor of Simon Tavaré
and Mike Waterman.
5-7-2012 We have moved into a newly renovated space on
the third floor of Herrin Labs! [Photos
(courtesy of MEI architects)]
4-5-2012 Undergraduate Amy Goldberg has been
awarded a National Science Foundation Graduate Research Fellowship. Amy
will be joining us at Stanford this autumn as a PhD student. Congrats
3-6-2012 Recent PhD
DeGiorgio received an Honorable Mention for the ProQuest
Distinguished Dissertation Award. The award recognizes outstanding
dissertations across all PhD programs at the University of Michigan.
1-1-2012 A recently published
of Shashir Reddy reports upper and lower bounds on the frequency of
the most frequent allele at a locus, conditional on the homozygosity and
number of distinct alleles of the locus (J Math Biol 64: 87-108).
This paper refines
an earlier study
that did not condition on the number of alleles, and it is one of several
articles in the lab to feature undergraduate
Past news items
SELECTED RECENT PUBLICATIONS
M Jakobsson, MD Edge, NA Rosenberg (2013) The
relationship between FST and the frequency of the
most frequent allele.
Genetics 193: 515-528.
JH Degnan, NA Rosenberg, T Stadler (2012) A
of the set of species trees that produce anomalous ranked gene trees.
IEEE/ACM Transactions on Computational Biology and Bioinformatics
TJ Pemberton, D Absher, MW Feldman, RM Myers, NA
Rosenberg, JZ Li (2012) Genomic patterns of homozygosity in worldwide
human populations. American Journal of Human Genetics 91:
Table 2 (.zip)]
Table 3 (.zip)]
Table 4 (.zip)]
Table 5 (.zip)]
S Ramachandran, NA Rosenberg (2011) A test of the influence
of continental axes of orientation on patterns of human gene flow.
American Journal of Physical Anthropology 146: 515-529.
ZA Szpiech, NA Rosenberg (2011) On the size
distribution of private microsatellite alleles. Theoretical
Population Biology 80: 100-113.
NA Rosenberg, L Huang*, EM Jewett*, ZA
Szpiech*, I Jankovic*, M Boehnke (2010) Genome-wide
association studies in diverse populations. Nature Reviews
Genetics 11: 356-366. [Abstract]
JT Mosher, TJ Pemberton, K Harter, C Wang,
EO Buzbas, P Dvorak, C Simon, SJ Morrison, NA Rosenberg
(2010) Lack of population diversity in commonly used human embryonic
stem-cell lines. New England Journal of Medicine 362: 183-185.
NM Kopelman, L Stone, C Wang, D Gefel, MW Feldman, J
Hillel, NA Rosenberg (2009) Genomic microsatellites identify
shared Jewish ancestry intermediate between Middle Eastern and
European populations. BMC Genetics 10: 80. [Abstract] [Full text at
journal website] [PDF]
M DeGiorgio, M Jakobsson, NA Rosenberg (2009)
Explaining worldwide patterns of human genetic variation using a
coalescent-based serial founder model of migration outward from
Africa. Proceedings of the National Academy of Sciences USA
M Jakobsson*, SW Scholz*, P Scheet*, JR Gibbs, JM
VanLiere, H-C Fung, ZA Szpiech, JH Degnan, K Wang, R
Guerreiro, JM Bras, JC Schymick, DG Hernandez, BJ Traynor, J
Simon-Sanchez, M Matarin, A Britton, J van de Leemput, I Rafferty, M
Bucan, HM Cann, JA Hardy, NA Rosenberg, AB Singleton (2008)
Genotype, haplotype and copy-number variation in worldwide human
populations. Nature 451: 998-1003. [Abstract] [PDF] [Supplement]