Craig Lowe

Positions:

Assistant Professor of Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2010

University of California - Santa Cruz

Grants:

From a Long List to Causal Variants: High-Throughput Gene Regulatory Assays in Developing Tissues

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

From a Long List to Causal Variants: High-Throughput Gene Regulatory Assays in Developing Tissues

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

From a Long List to Causal Variants: High-Throughput Gene Regulatory Assays in Developing Tissues

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

The Genetic Basis of Macroevolutionary Trends

Administered By
Molecular Genetics and Microbiology
Awarded By
University of Minnesota
Role
Principal Investigator
Start Date
End Date

Publications:

Corrigendum: Detecting differential copy number variation between groups of samples.

Authors
Lowe, CB; Sanchez-Luege, N; Howes, TR; Brady, SD; Daugherty, RR; Jones, FC; Bell, MA; Kingsley, DM
MLA Citation
Lowe, Craig B., et al. “Corrigendum: Detecting differential copy number variation between groups of samples.Genome Res, vol. 28, no. 5, May 2018, p. 766.1. Pubmed, doi:10.1101/gr.237370.118.
URI
https://scholars.duke.edu/individual/pub1427154
PMID
29717001
Source
pubmed
Published In
Genome Res
Volume
28
Published Date
Start Page
766.1
DOI
10.1101/gr.237370.118

A distal enhancer and an ultraconserved exon are derived from a novel retroposon.

Hundreds of highly conserved distal cis-regulatory elements have been characterized so far in vertebrate genomes. Many thousands more are predicted on the basis of comparative genomics. However, in stark contrast to the genes that they regulate, in invertebrates virtually none of these regions can be traced by using sequence similarity, leaving their evolutionary origins obscure. Here we show that a class of conserved, primarily non-coding regions in tetrapods originated from a previously unknown short interspersed repetitive element (SINE) retroposon family that was active in the Sarcopterygii (lobe-finned fishes and terrestrial vertebrates) in the Silurian period at least 410 million years ago (ref. 4), and seems to be recently active in the 'living fossil' Indonesian coelacanth, Latimeria menadoensis. Using a mouse enhancer assay we show that one copy, 0.5 million bases from the neuro-developmental gene ISL1, is an enhancer that recapitulates multiple aspects of Isl1 expression patterns. Several other copies represent new, possibly regulatory, alternatively spliced exons in the middle of pre-existing Sarcopterygian genes. One of these, a more than 200-base-pair ultraconserved region, 100% identical in mammals, and 80% identical to the coelacanth SINE, contains a 31-amino-acid-residue alternatively spliced exon of the messenger RNA processing gene PCBP2 (ref. 6). These add to a growing list of examples in which relics of transposable elements have acquired a function that serves their host, a process termed 'exaptation', and provide an origin for at least some of the many highly conserved vertebrate-specific genomic sequences.
Authors
Bejerano, G; Lowe, CB; Ahituv, N; King, B; Siepel, A; Salama, SR; Rubin, EM; Kent, WJ; Haussler, D
MLA Citation
Bejerano, Gill, et al. “A distal enhancer and an ultraconserved exon are derived from a novel retroposon.Nature, vol. 441, no. 7089, May 2006, pp. 87–90. Pubmed, doi:10.1038/nature04696.
URI
https://scholars.duke.edu/individual/pub1348812
PMID
16625209
Source
pubmed
Published In
Nature
Volume
441
Published Date
Start Page
87
End Page
90
DOI
10.1038/nature04696

Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution.

Direct comparisons of human and non-human primate brains can reveal molecular pathways underlying remarkable specializations of the human brain. However, chimpanzee tissue is inaccessible during neocortical neurogenesis when differences in brain size first appear. To identify human-specific features of cortical development, we leveraged recent innovations that permit generating pluripotent stem cell-derived cerebral organoids from chimpanzee. Despite metabolic differences, organoid models preserve gene regulatory networks related to primary cell types and developmental processes. We further identified 261 differentially expressed genes in human compared to both chimpanzee organoids and macaque cortex, enriched for recent gene duplications, and including multiple regulators of PI3K-AKT-mTOR signaling. We observed increased activation of this pathway in human radial glia, dependent on two receptors upregulated specifically in human: INSR and ITGB8. Our findings establish a platform for systematic analysis of molecular changes contributing to human brain development and evolution.
Authors
Pollen, AA; Bhaduri, A; Andrews, MG; Nowakowski, TJ; Meyerson, OS; Mostajo-Radji, MA; Di Lullo, E; Alvarado, B; Bedolli, M; Dougherty, ML; Fiddes, IT; Kronenberg, ZN; Shuga, J; Leyrat, AA; West, JA; Bershteyn, M; Lowe, CB; Pavlovic, BJ; Salama, SR; Haussler, D; Eichler, EE; Kriegstein, AR
MLA Citation
Pollen, Alex A., et al. “Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution.Cell, vol. 176, no. 4, Feb. 2019, pp. 743-756.e17. Pubmed, doi:10.1016/j.cell.2019.01.017.
URI
https://scholars.duke.edu/individual/pub1368734
PMID
30735633
Source
pubmed
Published In
Cell
Volume
176
Published Date
Start Page
743
End Page
756.e17
DOI
10.1016/j.cell.2019.01.017

Characterization of a Human-Specific Tandem Repeat Associated with Bipolar Disorder and Schizophrenia.

Bipolar disorder (BD) and schizophrenia (SCZ) are highly heritable diseases that affect more than 3% of individuals worldwide. Genome-wide association studies have strongly and repeatedly linked risk for both of these neuropsychiatric diseases to a 100 kb interval in the third intron of the human calcium channel gene CACNA1C. However, the causative mutation is not yet known. We have identified a human-specific tandem repeat in this region that is composed of 30 bp units, often repeated hundreds of times. This large tandem repeat is unstable using standard polymerase chain reaction and bacterial cloning techniques, which may have resulted in its incorrect size in the human reference genome. The large 30-mer repeat region is polymorphic in both size and sequence in human populations. Particular sequence variants of the 30-mer are associated with risk status at several flanking single-nucleotide polymorphisms in the third intron of CACNA1C that have previously been linked to BD and SCZ. The tandem repeat arrays function as enhancers that increase reporter gene expression in a human neural progenitor cell line. Different human arrays vary in the magnitude of enhancer activity, and the 30-mer arrays associated with increased psychiatric disease risk status have decreased enhancer activity. Changes in the structure and sequence of these arrays likely contribute to changes in CACNA1C function during human evolution and may modulate neuropsychiatric disease risk in modern human populations.
Authors
Song, JHT; Lowe, CB; Kingsley, DM
MLA Citation
Song, Janet H. T., et al. “Characterization of a Human-Specific Tandem Repeat Associated with Bipolar Disorder and Schizophrenia.Am J Hum Genet, vol. 103, no. 3, Sept. 2018, pp. 421–30. Pubmed, doi:10.1016/j.ajhg.2018.07.011.
URI
https://scholars.duke.edu/individual/pub1348817
PMID
30100087
Source
pubmed
Published In
Am J Hum Genet
Volume
103
Published Date
Start Page
421
End Page
430
DOI
10.1016/j.ajhg.2018.07.011

Detecting differential copy number variation between groups of samples.

We present a method to detect copy number variants (CNVs) that are differentially present between two groups of sequenced samples. We use a finite-state transducer where the emitted read depth is conditioned on the mappability and GC-content of all reads that occur at a given base position. In this model, the read depth within a region is a mixture of binomials, which in simulations matches the read depth more closely than the often-used negative binomial distribution. The method analyzes all samples simultaneously, preserving uncertainty as to the breakpoints and magnitude of CNVs present in an individual when it identifies CNVs differentially present between the two groups. We apply this method to identify CNVs that are recurrently associated with postglacial adaptation of marine threespine stickleback (Gasterosteus aculeatus) to freshwater. We identify 6664 regions of the stickleback genome, totaling 1.7 Mbp, which show consistent copy number differences between marine and freshwater populations. These deletions and duplications affect both protein-coding genes and cis-regulatory elements, including a noncoding intronic telencephalon enhancer of DCHS1 The functions of the genes near or included within the 6664 CNVs are enriched for immunity and muscle development, as well as head and limb morphology. Although freshwater stickleback have repeatedly evolved from marine populations, we show that freshwater stickleback also act as reservoirs for ancient ancestral sequences that are highly conserved among distantly related teleosts, but largely missing from marine stickleback due to recent selective sweeps in marine populations.
Authors
Lowe, CB; Sanchez-Luege, N; Howes, TR; Brady, SD; Daugherty, RR; Jones, FC; Bell, MA; Kingsley, DM
MLA Citation
Lowe, Craig B., et al. “Detecting differential copy number variation between groups of samples.Genome Res, vol. 28, no. 2, Feb. 2018, pp. 256–65. Pubmed, doi:10.1101/gr.206938.116.
URI
https://scholars.duke.edu/individual/pub1348808
PMID
29229672
Source
pubmed
Published In
Genome Res
Volume
28
Published Date
Start Page
256
End Page
265
DOI
10.1101/gr.206938.116

Research Areas:

Muser Mentor