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.
new study in PLoS
Genetics led by former postdoc Paul Verdu reports on
admixture in Native American and First Nation populations of the
Pacific Northwest. The study describes recent European admixture in
coastal and inland populations from British Columbia and Alaska, also
uncovering evidence of recent East Asian admixture in the inland
groups. It is the first genomic investigation focused on the Pacific
Northwest region. Former
Pemberton was a contributor to the project.
8-8-2014 We congratulate PhD student Ethan Jewett on
the defense of his thesis, "Models, tools, and approaches for studying
genetic and cultural variation." Ethan's thesis examines a series of
problems on coalescent lineage distributions, with applications to the
study of population growth and migration, inference of species trees, and
genotype imputation. He also conducts analyses of variation in word usage,
both in the United States and in Cape Verde, posing questions about
cultural evolution. Ethan's work has been recognized with the Department
of Biology's Samuel Karlin Prize in Mathematical Biology. Congratulations
Former postdoc Trevor
a study of
population-genetic factors that affect worldwide variation in the
inbreeding coefficent, showing that the value of this popular
population-genetic statistic increases with increased consanguinty
but also with measures that reflect decreasing genetic diversity
and increasing genetic isolation. The study is part of a special issue
of Human Heredity on Consanguinity and Genomics.
6-25-2014 We congratulate co-mentored graduate student
Dr. Naama Kopelman, on the completion of her PhD! Naama's thesis,
conducted at Tel Aviv University on "The complex genealogy of Jewish
populations," examines the genetic relationships of Jewish
populations using both microsatellite loci
 and genome-wide single
nucleotide polymorphisms . She also
performs a theoretical investigation of the effect of admixture on
tree-reconstruction algorithms, inspired by the placement of
Jewish populations in a neighbor-joining tree
. Naama has begun a
postdoc with Itay Mayrose, Department of Molecular Biology and
Ecology of Plants, Tel Aviv University.
6-22-2014 A new special issue of Human
Biology focuses on the genetics of Jewish populations. The lab
contributes to two research studies in the special issue:
new paper by former postdoc
determines the mean of the deep coalescence cost, measuring the fit of a
gene tree to a species tree, under probability distributions for the
shapes of gene trees and species trees. This paper extends Cuong's
previous analysis focusing on the maximum deep coalescence cost rather
than the mean . The
work advances knowledge of an important concept in estimation of species
3-29-2014 Former graduate
DeGiorgio has compared the properties of several different
methods for species tree inference, using sequence data from eight
species of North American
pines. The paper
support theoretical work from the lab on properties of the deep coalescence cost
 and extend the lab's work on
trees and species trees.
- In a study of
Y-chromosomal lineages in the Samaritans, Oefner et al. find
that most Samaritans have a distinctive Y chromosome similar to that
of Jewish Cohen lineages. Curiously, among the Samaritans, the only
exception distant from the Cohen model haplotype is that of the
Samaritan Cohen lineage.
- An international team including graduate student Naama Kopelman
studies genetic relationships with the Ashkenazi Jewish population in a
large genome-wide data
set, finding considerable
shared ancestry with other Jewish populations and tracing more distant
relationships to other populations of Europe and the Middle East.
to the special issue, by Noah
Rosenberg and Steven Weitzman.
3-14-2014 Graduate student Ethan Jewett has
summarized and enhanced results on the properties of the number of
lineages in genealogies obtained under the coalescent model. His work
produces new approximations that can facilitate uses of the coalescent
in large samples and complex demographies. The
article appears in
the May 2014 issue of
Theoretical Population Biology.
2-5-2014 A new
paper in the IEEE/ACM
Transactions on Computational Biology and Bioinformatics describes
the properties of coalescent histories for gene trees and species trees
that resemble the "caterpillar" shape. The work extends earlier projects
from the lab on coalescent histories
, and it advances the lab's
research program on the
combinatorics of evolutionary trees.
1-2-2014 Former graduate
DeGiorgio has started a lab as Assistant Professor of Biology at
Pennsylvania State University. We wish him all the best in his new position!
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
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.
appears online 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
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.
Past news items
SELECTED RECENT PUBLICATIONS
M DeGiorgio, J Syring, AJ Eckert, AI Liston, R Cronn, DB
Neale, NA Rosenberg (2014) An empirical evaluation of two-stage
species tree inference strategies using a multilocus dataset from North
American pines. BMC Evolutionary Biology 14: 67.
File 1 (.xlsx, accession numbers)]
File 2 (.pdf, supplementary analyses)]
File 3 (.zip, data)]
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]