Huntington F. Willard

A national clinical decision support infrastructure to enable the widespread and consistent practice of genomic and personalized medicine (2009)

Kawamoto, Kensaku, Lobach, David F, Willard, Huntington F, Ginsburg, Geoffrey S

Abstract Background In recent years, the completion of the Human Genome Project and other rapid advances in genomics have led to increasing anticipation of an era of genomic and personalized...

Development and application of a phylogenomic toolkit: Resolving the evolutionary history of Madagascar's lemurs (2008)

Horvath, Julie E., Weisrock, David W., Embry, Stephanie L., Fiorentino, Isabella, Balhoff, James P., Kappeler, Peter, ...

Lemurs and the other strepsirrhine primates are of great interest to the primate genomics community due to their phylogenetic placement as the sister lineage to all other primates. Previous attempts...

Evidence of Influence of Genomic DNA Sequence on Human X Chromosome Inactivation (2006)

Zhong Wang, Huntington F. Willard, Sayan Mukherjee, Terrence S. Furey

A significant number of human X-linked genes escape X chromosome inactivation and are thus expressed from both the active and inactive X chromosomes. The basis for escape from inactivation and the...

Evidence of Influence of Genomic DNA Sequence on Human X Chromosome Inactivation (2006)

Zhong Wang, Huntington F Willard, Sayan Muhkerjee, Terrence Furey

A significant number of human X-linked genes escape X chromosome inactivation and are thus expressed from both the active and inactive X chromosomes. The basis for escape from inactivation and the...

Genetic control of X chromosome inactivation in mice: definition of the Xce candidate interval. (2006)

Chadwick, Lisa Helbling, Pertz, Lisa M., Broman, Karl W., Bartolomei, Marisa S., Willard, Huntington F.

In early mammalian development, one of the two X chromosomes is silenced in each female cell as a result of X chromosome inactivation, the mammalian dosage compensation mechanism. In the mouse...

X chromosome-inactivation patterns of 1,005 phenotypically unaffected females. (2006)

Amos-Landgraf, James M., Cottle, Amy, Plenge, Robert M., Friez, Mike, Schwartz, Charles E., Longshore, John, ...

X-chromosome inactivation is widely believed to be random in early female development and to result in a mosaic distribution of cells, approximately half with the paternally derived X chromosome...

Chromosome-wide, allele-specific analysis of the histone code on the human X chromosome (2006)

Valley, Cory M., Pertz, Lisa M., Balakumaran, Bala S., Willard, Huntington F.

Variation in the composition of chromatin has been proposed to generate a ‘histone code’ that epigenetically regulates gene expression in a variety of eukaryotic systems. As a result of the...

Chromosome-wide, Allele-specific Analysis of the Histone Code on the Human X Chromosome (2006)

Valley, Cory M., Pertz, Lisa M., Balakumaran, Bala S., Willard, Huntington F.

Variation in the composition of chromatin has been proposed to generate a ‘histone code’ that epigenetically regulates gene expression in a variety of eukaryotic systems. As a result of the...

The evolutionary dynamics of {alpha}-satellite (2006)

Rudd, M. Katharine, Wray, Gregory A., Willard, Huntington F.

α-Satellite is a family of tandemly repeated sequences found at all normal human centromeres. In addition to its significance for understanding centromere function, α-satellite is also a model for...

Efficient assembly of de novohuman artificial chromosomes from large genomic loci (2005)

Basu, Joydeep, Compitello, George, Stromberg, Gregory, Willard, Huntington F, Van Bokkelen, Gil

Abstract Background Human Artificial Chromosomes (HACs) are potentially useful vectors for gene transfer studies and for functional annotation of the genome because of their suitability for cloning,...

Progressive proximal expansion of the primate X chromosome centromere. (2005)

Schueler, Mary G., Dunn, John M., Bird, Christine P., Ross, Mark T., Viggiano, Luigi, ...

Previous studies of the pericentromeric region of the human X chromosome short arm (Xp) revealed an age gradient from ancient DNA that contains expressed genes to recent human-specific DNA at the...

The evolutionary dynamics of {alpha}-satellite (2005)

Rudd, M. Katharine, Wray, Gregory A., Willard, Huntington F.

α-satellite is a family of tandemly repeated sequences found at all normal human centromeres. In addition to its significance for understanding centromere function, α-satellite is also a model for...

Rapid creation of BAC-based human artificial chromosome vectors by transposition with synthetic alpha-satellite arrays (2005)

Basu, Joydeep, Stromberg, Gregory, Compitello, George, Willard, Huntington F., Bokkelen, Gil Van

Efficient construction of BAC-based human artificial chromosomes (HACs) requires optimization of each key functional unit as well as development of techniques for the rapid and reliable manipulation...

Assembly and characterization of heterochromatin and euchromatin on human artificial chromosomes (2004)

Grimes, Brenda R, Babcock, Jennifer, Rudd, M Katharine, Chadwick, Brian, Willard, Huntington F

Abstract Background Human centromere regions are characterized by the presence of alpha-satellite DNA, replication late in S phase and a heterochromatic appearance. Recent models propose that the...

Assembly and characterization of heterochromatin and euchromatin on human artificial chromosomes. (2004)

Grimes, Brenda R, Babcock, Jennifer, Rudd, M Katharine, Chadwick, Brian, Willard, Huntington F

BACKGROUND: Human centromere regions are characterized by the presence of alpha-satellite DNA, replication late in S phase and a heterochromatic appearance. Recent models propose that the centromere...

Human artificial chromosomes with alpha satellite-based de novo centromeres show increased frequency of nondisjunction and anaphase lag. (2003)

Rudd, M. Katharine, Mays, Robert W., Schwartz, Stuart, Willard, Huntington F.

Human artificial chromosomes have been used to model requirements for human chromosome segregation and to explore the nature of sequences competent for centromere function. Normal human centromeres...

Chromatin of the Barr body: Histone and non-histone proteins associated with or excluded from the inactive X chromosome (2003)

Chadwick, Brian P., Willard, Huntington F.

The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the...

Chromatin of the Barr body: histone and non-histone proteins associated with or excluded from the inactive X chromosome (2003)

Chadwick, Brian P., Willard, Huntington F.

The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the...

Chromatin of the Barr body: Histone and non-histone proteins associated with or excluded from the inactive X chromosome (2003)

Chadwick, Brian P., Willard, Huntington F.

The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the...

An ectopic human XIST gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells (2002)

Hall, Lisa L., Byron, Meg, Sakai, Kosuke, Carrel, Laura, Willard, Huntington F., Lawrence, Jeanne B.

It has been believed that XIST RNA requires a discrete window in early development to initiate the series of chromatin-remodeling events that form the heterochromatic inactive X chromosome. Here we...

Artificial mammalian chromosome (2002)

Harrington, John J., Van Bokkelen, Gil B., Willard, Huntington F.

Field of the invention: The invention relates to the field of gene expression and gene therapy, and to novel vectors for these uses. In particular, the invention relates to the development and use of...

Artificial mammalian chromosome (2002)

Harrington, John J., Van Bokkelen, Gil B., Willard, Huntington F.

Field of the invention: The invention relates to the field of gene expression and gene therapy, and to novel vectors for these uses. In particular, the invention relates to the development and use of...

An ectopic human XIST gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells. (2002)

Hall, Lisa L., Byron, Meg, Sakai, Kosuke, Carrel, Laura, Willard, Huntington F., Lawrence, Jeanne B.

It has been believed that XIST RNA requires a discrete window in early development to initiate the series of chromatin-remodeling events that form the heterochromatic inactive X chromosome. Here we...

Skewed X-chromosome inactivation is a common feature of X-linked mental retardation disorders. (2002)

Plenge, Robert M., Stevenson, Roger A., Lubs, Herbert A., Schwartz, Charles E., Willard, Huntington F.

Some deleterious X-linked mutations may result in a growth disadvantage for those cells in which the mutation, when on the active X chromosome, affects cell proliferation or viability. To explore the...

Cell cycle-dependent localization of macroH2A in chromatin of the inactive X chromosome. (2002)

Chadwick, Brian P., Willard, Huntington F.

One of several features acquired by chromatin of the inactive X chromosome (Xi) is enrichment for the core histone H2A variant macroH2A within a distinct nuclear structure referred to as a...

Histone variant macroH2A contains two distinct macrochromatin domains capable of directing macroH2A to the inactive X chromosome. (2001)

Chadwick, Brian P., Valley, Cory M., Willard, Huntington F.

Chromatin on the inactive X chromosome (Xi) of female mammals is enriched for the histone variant macroH2A that can be detected at interphase as a distinct nuclear structure referred to as a macro...

A novel chromatin protein, distantly related to histone H2A, is largely excluded from the inactive X chromosome. (2001)

Chadwick, Brian P., Willard, Huntington F.

Chromatin on the mammalian inactive X chromosome differs in a number of ways from that on the active X. One protein, macroH2A, whose amino terminus is closely related to histone H2A, is enriched on...

Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant (2001)

Chadwick, Brian P., Willard, Huntington F.

MacroH2A1 is an unusual variant of the core histone H2A which is enriched in chromatin on the inactive X chromosome of female mammals. The N-terminal third of the protein shares 65% amino acid...

Histone variant macroH2A contains two distinct macrochromatin domains capable of directing macroH2A to the inactive X chromosome (2001)

Chadwick, Brian P., Valley, Cory M., Willard, Huntington F.

Chromatin on the inactive X chromosome (Xi) of female mammals is enriched for the histone variant macroH2A that can be detected at interphase as a distinct nuclear structure referred to as a macro...

Method for stably cloning large repeating DNA sequences (1999)

Harrington, John J., Van Bokkelen, Gil B., Willard, Huntington F.

Field of the invention: This invention relates to the field of gene therapy and gene therapy vector technology. It relates to the development and use of synthetic human chromosomes, or synthetic...

Method for stably cloning large repeating DNA sequences (1999)

Harrington, John J., Van Bokkelen, Gil B., Willard, Huntington F.

Field of the invention: This invention relates to the field of gene therapy and gene therapy vector technology. It relates to the development and use of synthetic human chromosomes, or synthetic...

A first-generation X-inactivation profile of the human X chromosome. (1999)

Carrel, Laura, Cottle, Amy A., Goglin, Karrie C., Willard, Huntington F.

In females, most genes on the X chromosome are generally assumed to be transcriptionally silenced on the inactive X as a result of X inactivation. However, particularly in humans, an increasing...

Heterogeneous gene expression from the inactive X chromosome: an X-linked gene that escapes X inactivation in some human cell lines but is inactivated in others. (1999)

Carrel, Laura, Willard, Huntington F.

In mammalian females, most genes on one X chromosome are transcriptionally silenced as a result of X chromosome inactivation. Whereas it is well established that some X-linked genes "escape" X...

Chromosomal basis of X chromosome inactivation: identification of a multigene domain in Xp11.21-p11.22 that escapes X inactivation. (1998)

Miller, Andrew P., Willard, Huntington F.

A number of genes have been identified that escape mammalian X chromosome inactivation and are expressed from both active and inactive X chromosomes. The basis for escape from inactivation is unknown...

Method for stably cloning large repeating units of DNA (1997)

Van Bokkelen, Gil B., Harrington, John J., Willard, Huntington F.

Field of the invention: This invention relates to the field of gene therapy and gene therapy vector technology. It also relates to the development and practical use of synthetic human chromosomes, or...

Method for stably cloning large repeating units of DNA (1997)

Van Bokkelen, Gil B., Harrington, John J., Willard, Huntington F.

Field of the invention: This invention relates to the field of gene therapy and gene therapy vector technology. It also relates to the development and practical use of synthetic human chromosomes, or...

X inactivation analysis and DNA methylation studies of the ubiquitin activating enzyme E1 and PCTAIRE-1 genes in human and mouse (1996)

Carrel, Laura, Clemson, Christine Moulton, Dunn, John M., Miller, Andrew P., Hunt, Patricia A., Lawrence, Jeanne B., ...

Previously reported data on the X inactivation status of the ubiquitin activating enzyme E1 (UBE1) gene have been contradictory, and the issue has remained unsettled. Here we present three lines of...

XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure (1996)

Clemson, Christine Moulton, McNeil, John A., Willard, Huntington F., Lawrence, Jeanne B.

The XIST gene is implicated in X chromosome inactivation, yet the RNA contains no apparent open reading frame. An accumulation of XIST RNA is observed near its site of transcription, the inactive X...

Three genes that escape X chromosome inactivation are clustered within a 6 Mb YAC contig and STS map in Xp11.21-p11.22 (1995)

Miller, Andrew P., Gustashaw, Karen, Wolff, Daynna J., Rider, Sue H., Monaco, Anthony P., Eble, Brian, ...

In order to study the distribution of genes that escape X chromosome inactivation, a high density yeast artificial chromosome (YAC) contig and STS map spanning approximately 6 Mb has been constructed...

The DXS423E gene in Xp11.21 escapes X chromosome inactivation (1995)

Brown, Carolyn J., Miller, Andrew P., Carrel, Laura, Rupert, Jim L., Davies, Kay E., Willard, Huntington F.

The DXS423E gene has been localized to Xp11.21 and is expressed in somatic cell hybrids retaining either the human active or inactive X chromosome, demonstrating that DXS423E escapes X chromosome...

The mouse Sb1.8 gene located at the distal end of the X chromosome is subject to X inactivation (1995)

Sultana, Razla, Adler, David A., Edelhoff, Susanne, Carrel, Laura, Lee, Kwang Ho, Chapman, Verne C., ...

The mouse homolog of the human DXS423E (SB1.8) gene has been isolated by screening a mouse cDNA library. Like its human counterpart, the mouse Sb1.8 gene is X-linked, as shown by Southern blot...

A novel transmembrane transporter encoded by the XPCT gene in Xq13.2 (1994)

Lafrenière, Ronald G., Carrel, Laura, Willard, Huntington F.

To study the regulation and chromosomal basis of X chromosome inactivation, we have physically characterized the region in Xq13.2 known to contain the X inactivation center (XIC), a locus required in...

Duplicated zinc finger protein genes on the proximal short arm of the human X chromosome: isolation, characterization and X-inactivation studies (1993)

Grelg, Gillian M., Sharp, Cecll B., Carrel, Laura, Willard, Huntington F.

Two highly similar zinc finger genes, ZXDA (Zinc finger, X-linked, Duplicated) and ZXDB, have been isolated and characterized. Both map to the proximal short arm region of the human X chromosome,...

A polymorphic X-linked tetranucleotide repeat locus displaying a high rate of new mutation: implications for mechanisms of mutation at short tandem repeat loci (1993)

Mahtani, Melanie M., Willard, Huntington F.

We report a high rate of new mutation at a short tandem repeat sequence polymorphism (STR, microsatellite) at locus DXS981 on the proximal long arm of the human X chromosome. Among individuals of the...

Evolutionary conservation of possible functional domains of the human and murine XIST genes (1993)

Hendrich, Brian D., Brown, Carolyn J., Willard, Huntington F.

The human XIST gene, a candidate for a role in X chromosome inactivation, has recently been cloned and sequenced, yielding a 17 kb cDNA with no apparent significant, conserved open reading frame. In...

Mapping of the distal boundary of the X-inactivation center in a rearranged X chromosome from a female expressing XIST (1993)

Lepplg, Kathleen A., Brown, Carolyn J., Bressler, Steven L., Gustashaw, Karen, Pagon, Roberta A., Willard, Huntington F., ...

A female patient with primary amenorrhea, Immature secondary sexual characteristics, and tall stature was found to have a normal X chromosome and a rearranged X [rea(X)] chromosome that resembled an...

The interleukin-2 receptor {gamma} chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1 (1993)

Puck, Jennifer M., Deschenes, Suzanne M., Porter, Joanne C., Dutra, Amalla S., Brown, Carolyn J., Willard, Huntington F., ...

The gene encoding the γ chain of the lymphocyte interleukin-2 receptor has been cloned and shown to be required to associate with the β chain in order for IL-2 internalization and cell activation...

2.6 Mb YAC contig of the human X inactivation center region in Xq13: physical linkage of the RPS4X, PHKA1, XIST and DXS128E genes (1993)

Lafrenlère, Ronald G., Brown, Carolyn J., Rider, Sue, Chelly, Jamel, Taillon-Miller, Patricia, Chinault, A.Craig, ...

X chromosome inactivation is a mechanism of dosage compensation that regulates the expression of mammalian X-linked genes between XY males and XX females. This phenomenon Is cis-acting, clonally...

The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus (1992)

Brown, Carolyn J., Hendrich, Brian D., Rupert, Jim L., Lafreniere, Ronald G., Xing, Yigong P., Lawrence, Jeanne B., ...

X chromosome inactivation in mammalian females results in the cis-limited transcriptional inactivity of most of the genes on one X chromosome. The XIST gene is unique among X-linked genes in being...

Refined localization of human connexin32 gene locus, GJB1, to Xq13.1 (1992)

Corcos, Isabel A., Lafreniere, Ronald G., Begy, Catherine R., Loch-Caruso, Rita, Willard, Huntington F., Glover, Thomas W.

Connexins are the peptide subunits of gap junctions that interconnect cells to allow the direct, intercellular transfer of small molecules. Recently, the human connexin32 gene (locus designation...

Assignment of human erythroid [delta]-aminolevulinate synthase (ALAS2) to a distal subregion of band Xp11.21 by PCR analysis of somatic cell hybrids containing X;Autosome translocations (1992)

Cotter, Philip D., Willard, Huntington F., Gorski, Jerome L., Bishop, David F.

The erythroid-specific (ALAS2) and housekeeping (ALAS1) genes encoding [delta]-aminolevulinate synthase have recently been mapped to chromosomes Xq21.1-->q21 and 3p21, respectively. The...

PCR amplification of tandemly repeated DNA: analysis of intra- and interchromosomal sequence variation and homologous unequal crossing-over in human alpha satellite DNA (1992)

Warburton, Peter E., Willard, Huntington F.

Tandemly repeated DNA can comprise several percent of total genomic DNA in complex organisms and, in some instances, may play a role in chromosome structure or function. Alpha satellite DNA is the...

A highly polymorphic dinucleotide repeat on the proximal short arm of the human X chromosome: linkage mapping of the synapsin I/A-raf-1 genes (1991)

Kirchgessner, Cordula U., Trofatter, James A., Mahtani, Melanie M., Willard, Huntington F., DeGennaro, Louis J.

A compound (AC)n repeat located 1,000 bp downstream from the human synapsin I gene and within the last intron of the A-raf-1 gene has been identified. DNA data-base comparisons of the sequences...

Physical map of the centromeric region of human chromosome 7: relationship between two distinct alpha satellite arrays (1991)

Wevrick, Rachel, Willard, Huntington F.

A long-range physical map of the centromeric region of human chromosome 7 has been constructed in order to define the region containing sequences with potential involvement in centromere function....

Linkage of the multiple endocrine neoplasia type 2B gene (MEN2B) to chromosome 10 markers linked to MEN2A (1990)

Norum, Robert A., Lafreniere, Ronald G., O'Neal, Lawrence W., Nikolai, Thomas F., Delaney, J. P., Sisson, James C., ...

The syndrome of multiple endocrine neoplasia type 2B (MEN 2B) resembles that of MEN 2A in that both include medullary carcinoma of the thyroid, pheochromocytoma, and autosomal dominant inheritance,...

X chromosome inactivation of the human TIMP gene (1990)

Brown, Carolyn J., FIenniken, Ann M., Williams, Bryan R.G., Willard, Huntington F.

X chromosome inactivation results in the cis-limited inactivation of most, but not all, genes on one of the two X chromosomes in mammalian females. The molecular basis for inactivation is unknown. In...

Nucleotide sequence heterogeneity of alpha satellite repetitive DNA: a survey of alphoid sequences from different human chromosomes (1987)

Waye, John S., Willard, Huntington F.

The human alpha satellite DNA family is composed of diverse, tandemly reiterated monomer units of −171 basepairs localized to the centromeric region of each chromosome. These sequences are...

Molecular analysis of a deletion polymorphism in alpha satellite of human chromosome 17: evidence for homologous unequal crossing-over and subsequent fixation (1986)

Waye, John S., Willard, Huntington F.

The human alpha satellite DNA family is organized into chromosome-specific subsets characterized by distinct higher-order repeats based an a {small tilde}171 basepair monomer unit. On human...

Chromosome-specific alpha satellite DNA: nucleotide sequence analysis of the 2.0 kilobasepair repeat from the human X chromosome (1985)

Waye, John S., Willard, Huntington F.

The pericentromeric region of the human X chromosome is characterized by a tandemly repeated family of 2.0 kilobasepair (kb) DNA fragments, initially revealed by cleavage of human DNA with the...

Isolation and characterization of a major tandem repeat family from the human X chromosome (1983)

Willard, Huntington F., Smith, Kirby D., Sutherland, Joanne

We report the Identification and characterization of a family of repeated restriction fragments whose molecular organization is apparently specific to the human X chromosome. This fragment,...

Isolation and characterization of cloned human DNA fragments carrying reiterated sequences common to both autosomes and the X chromosome (1981)

Schmeckpeper, Barbara J., Willard, Huntington F., Smith, Kirby D.

Several recombinants were identified and purified from a cloned library of human DNA by virtue of their homology to DNA from a mouse-human hybrid cell line containing a single human chromosome, the...

Chromosomal basis of X chromosome inactivation: Identification of a multigene domain in Xp11.21-p11.22 that escapes X inactivation

Miller, Andrew P., Willard, Huntington F.

A number of genes have been identified that escape mammalian X chromosome inactivation and are expressed from both active and inactive X chromosomes. The basis for escape from inactivation is unknown...

Heterogeneous gene expression from the inactive X chromosome: An X-linked gene that escapes X inactivation in some human cell lines but is inactivated in others

Carrel, Laura, Willard, Huntington F.

In mammalian females, most genes on one X chromosome are transcriptionally silenced as a result of X chromosome inactivation. Whereas it is well established that some X-linked genes “escape” X...

A first-generation X-inactivation profile of the human X chromosome

Carrel, Laura, Cottle, Amy A., Goglin, Karrie C., Willard, Huntington F.

In females, most genes on the X chromosome are generally assumed to be transcriptionally silenced on the inactive X as a result of X inactivation. However, particularly in humans, an increasing...

Histone variant macroH2A contains two distinct macrochromatin domains capable of directing macroH2A to the inactive X chromosome

Chadwick, Brian P., Valley, Cory M., Willard, Huntington F.

Chromatin on the inactive X chromosome (Xi) of female mammals is enriched for the histone variant macroH2A that can be detected at interphase as a distinct nuclear structure referred to as a macro...

An ectopic human XIST gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells

Hall, Lisa L., Byron, Meg, Sakai, Kosuke, Carrel, Laura, Willard, Huntington F., Lawrence, Jeanne B.

It has been believed that XIST RNA requires a discrete window in early development to initiate the series of chromatin-remodeling events that form the heterochromatic inactive X chromosome. Here we...

Human Artificial Chromosomes with Alpha Satellite-Based De Novo Centromeres Show Increased Frequency of Nondisjunction and Anaphase Lag

Rudd, M. Katharine, Mays, Robert W., Schwartz, Stuart, Willard, Huntington F.

Human artificial chromosomes have been used to model requirements for human chromosome segregation and to explore the nature of sequences competent for centromere function. Normal human centromeres...

Inherited Methylmalonyl CoA Mutase Apoenzyme Deficiency in Human Fibroblasts: EVIDENCE FOR ALLELIC HETEROGENEITY, GENETIC COMPOUNDS, AND CODOMINANT EXPRESSION

Willard, Huntington F., Rosenberg, Leon E.

We have measured and characterized methylmalonyl coenzyme A (CoA) mutase activity in extracts of cultured human fibroblasts from 23 patients with inherited deficiency of the mutase apoenzyme and from...

Cobalamin Binding and Cobalamin-Dependent Enzyme Activity in Normal and Mutant Human Fibroblasts

Mellman, Ira, Willard, Huntington F., Rosenberg, Leon E.

We have studied the intracellular binding of radioactive cobalamin by normal cultured human fibroblasts grown in medium containing [57Co]-cobalamin. We have also assessed the significance of defects...

Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome

Chadwick, Brian P., Willard, Huntington F.

Heterochromatin is defined classically by condensation throughout the cell cycle, replication in late S phase and gene inactivity. Facultative heterochromatin is of particular interest, because its...

Assembly and characterization of heterochromatin and euchromatin on human artificial chromosomes

Grimes, Brenda R, Babcock, Jennifer, Rudd, M Katharine, Chadwick, Brian, Willard, Huntington F

An assay of the formation of heterochromatin and euchromatin on de novo human artificial chromosomes containing alpha satellite DNA revealed that only a small amount of heterochromatin may be...

Rapid creation of BAC-based human artificial chromosome vectors by transposition with synthetic alpha-satellite arrays

Basu, Joydeep, Stromberg, Gregory, Compitello, George, Willard, Huntington F., Bokkelen, Gil Van

Efficient construction of BAC-based human artificial chromosomes (HACs) requires optimization of each key functional unit as well as development of techniques for the rapid and reliable manipulation...

Progressive proximal expansion of the primate X chromosome centromere

Schueler, Mary G., Dunn, John M., Bird, Christine P., Ross, Mark T., Viggiano, Luigi, Rocchi, Mariano, ...

Previous studies of the pericentromeric region of the human X chromosome short arm (Xp) revealed an age gradient from ancient DNA that contains expressed genes to recent human-specific DNA at the...

The evolutionary dynamics of α-satellite

Rudd, M. Katharine, Wray, Gregory A., Willard, Huntington F.

α-Satellite is a family of tandemly repeated sequences found at all normal human centromeres. In addition to its significance for understanding centromere function, α-satellite is also a model for...

An N-ethyl-N-nitrosourea mutagenesis screen for epigenetic mutations in the mouse.

Percec, Ivona, Thorvaldsen, Joanne L, Plenge, Robert M, Krapp, Christopher J, Nadeau, Joseph H, Willard, Huntington F, ...

The mammalian epigenetic phenomena of X inactivation and genomic imprinting are incompletely understood. X inactivation equalizes X-linked expression between males and females by silencing genes on...

Evidence of Influence of Genomic DNA Sequence on Human X Chromosome Inactivation

Wang, Zhong, Willard, Huntington F, Mukherjee, Sayan, Furey, Terrence S

A significant number of human X-linked genes escape X chromosome inactivation and are thus expressed from both the active and inactive X chromosomes. The basis for escape from inactivation and the...

Genetic Control of X Chromosome Inactivation in Mice: Definition of the Xce Candidate Interval

Chadwick, Lisa Helbling, Pertz, Lisa M., Broman, Karl W., Bartolomei, Marisa S., Willard, Huntington F.

In early mammalian development, one of the two X chromosomes is silenced in each female cell as a result of X chromosome inactivation, the mammalian dosage compensation mechanism. In the mouse...

The human ryanodine receptor gene: Its mapping to 19q13.1, placement in a chromosome 19 linkage group, and exclusion as the gene causing myotonic dystrophy

MacKenzie, Alex E., Korneluk, Robert G., Zorzato, Francesco, Fujii, Junichi, Phillips, Michael, Iles, David, ...

The recent cloning of cDNA encoding the Ca++ release channel (ryanodine receptor) of human sarcoplasmic reticulum has enabled us to use somatic cell hybrids to localize the ryanodine receptor gene...

Chromosomal basis of X chromosome inactivation: Identification of a multigene domain in Xp11.21-p11.22 that escapes X inactivation

Miller, Andrew P., Willard, Huntington F.

A number of genes have been identified that escape mammalian X chromosome inactivation and are expressed from both active and inactive X chromosomes. The basis for escape from inactivation is unknown...

Heterogeneous gene expression from the inactive X chromosome: An X-linked gene that escapes X inactivation in some human cell lines but is inactivated in others

Carrel, Laura, Willard, Huntington F.

In mammalian females, most genes on one X chromosome are transcriptionally silenced as a result of X chromosome inactivation. Whereas it is well established that some X-linked genes “escape” X...

A first-generation X-inactivation profile of the human X chromosome

Carrel, Laura, Cottle, Amy A., Goglin, Karrie C., Willard, Huntington F.

In females, most genes on the X chromosome are generally assumed to be transcriptionally silenced on the inactive X as a result of X inactivation. However, particularly in humans, an increasing...

Histone variant macroH2A contains two distinct macrochromatin domains capable of directing macroH2A to the inactive X chromosome

Chadwick, Brian P., Valley, Cory M., Willard, Huntington F.

Chromatin on the inactive X chromosome (Xi) of female mammals is enriched for the histone variant macroH2A that can be detected at interphase as a distinct nuclear structure referred to as a macro...

An ectopic human XIST gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells

Hall, Lisa L., Byron, Meg, Sakai, Kosuke, Carrel, Laura, Willard, Huntington F., Lawrence, Jeanne B.

It has been believed that XIST RNA requires a discrete window in early development to initiate the series of chromatin-remodeling events that form the heterochromatic inactive X chromosome. Here we...

Human Artificial Chromosomes with Alpha Satellite-Based De Novo Centromeres Show Increased Frequency of Nondisjunction and Anaphase Lag

Rudd, M. Katharine, Mays, Robert W., Schwartz, Stuart, Willard, Huntington F.

Human artificial chromosomes have been used to model requirements for human chromosome segregation and to explore the nature of sequences competent for centromere function. Normal human centromeres...

Inherited Methylmalonyl CoA Mutase Apoenzyme Deficiency in Human Fibroblasts: EVIDENCE FOR ALLELIC HETEROGENEITY, GENETIC COMPOUNDS, AND CODOMINANT EXPRESSION

Willard, Huntington F., Rosenberg, Leon E.

We have measured and characterized methylmalonyl coenzyme A (CoA) mutase activity in extracts of cultured human fibroblasts from 23 patients with inherited deficiency of the mutase apoenzyme and from...

Cobalamin Binding and Cobalamin-Dependent Enzyme Activity in Normal and Mutant Human Fibroblasts

Mellman, Ira, Willard, Huntington F., Rosenberg, Leon E.

We have studied the intracellular binding of radioactive cobalamin by normal cultured human fibroblasts grown in medium containing [57Co]-cobalamin. We have also assessed the significance of defects...

Skewed X-Chromosome Inactivation Is a Common Feature of X-Linked Mental Retardation Disorders

Plenge, Robert M., Stevenson, Roger A., Lubs, Herbert A., Schwartz, Charles E., Willard, Huntington F.

Some deleterious X-linked mutations may result in a growth disadvantage for those cells in which the mutation, when on the active X chromosome, affects cell proliferation or viability. To explore the...

Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome

Chadwick, Brian P., Willard, Huntington F.

Heterochromatin is defined classically by condensation throughout the cell cycle, replication in late S phase and gene inactivity. Facultative heterochromatin is of particular interest, because its...

Assembly and characterization of heterochromatin and euchromatin on human artificial chromosomes

Grimes, Brenda R, Babcock, Jennifer, Rudd, M Katharine, Chadwick, Brian, Willard, Huntington F

An assay of the formation of heterochromatin and euchromatin on de novo human artificial chromosomes containing alpha satellite DNA revealed that only a small amount of heterochromatin may be...

Rapid creation of BAC-based human artificial chromosome vectors by transposition with synthetic alpha-satellite arrays

Basu, Joydeep, Stromberg, Gregory, Compitello, George, Willard, Huntington F., Bokkelen, Gil Van

Efficient construction of BAC-based human artificial chromosomes (HACs) requires optimization of each key functional unit as well as development of techniques for the rapid and reliable manipulation...

Progressive proximal expansion of the primate X chromosome centromere

Schueler, Mary G., Dunn, John M., Bird, Christine P., Ross, Mark T., Viggiano, Luigi, Rocchi, Mariano, ...

Previous studies of the pericentromeric region of the human X chromosome short arm (Xp) revealed an age gradient from ancient DNA that contains expressed genes to recent human-specific DNA at the...

The evolutionary dynamics of α-satellite

Rudd, M. Katharine, Wray, Gregory A., Willard, Huntington F.

α-Satellite is a family of tandemly repeated sequences found at all normal human centromeres. In addition to its significance for understanding centromere function, α-satellite is also a model for...

An N-ethyl-N-nitrosourea mutagenesis screen for epigenetic mutations in the mouse.

Percec, Ivona, Thorvaldsen, Joanne L, Plenge, Robert M, Krapp, Christopher J, Nadeau, Joseph H, Willard, Huntington F, ...

The mammalian epigenetic phenomena of X inactivation and genomic imprinting are incompletely understood. X inactivation equalizes X-linked expression between males and females by silencing genes on...

Evidence of Influence of Genomic DNA Sequence on Human X Chromosome Inactivation

Wang, Zhong, Willard, Huntington F, Mukherjee, Sayan, Furey, Terrence S

A significant number of human X-linked genes escape X chromosome inactivation and are thus expressed from both the active and inactive X chromosomes. The basis for escape from inactivation and the...

Genetic Control of X Chromosome Inactivation in Mice: Definition of the Xce Candidate Interval

Chadwick, Lisa Helbling, Pertz, Lisa M., Broman, Karl W., Bartolomei, Marisa S., Willard, Huntington F.

In early mammalian development, one of the two X chromosomes is silenced in each female cell as a result of X chromosome inactivation, the mammalian dosage compensation mechanism. In the mouse...

The human ryanodine receptor gene: Its mapping to 19q13.1, placement in a chromosome 19 linkage group, and exclusion as the gene causing myotonic dystrophy

MacKenzie, Alex E., Korneluk, Robert G., Zorzato, Francesco, Fujii, Junichi, Phillips, Michael, Iles, David, ...

The recent cloning of cDNA encoding the Ca++ release channel (ryanodine receptor) of human sarcoplasmic reticulum has enabled us to use somatic cell hybrids to localize the ryanodine receptor gene...

Genetic analysis of eight loci tightly linked to neurofibromatosis 1

Stephens, Karen, Green, Philip, Riccardi, Vincent M., Ng, Siu, Rising, Marcia, Barker, David, ...

The genetic locus for neurofibromatosis 1 (NF1) has recently been mapped to the pericentromeric region of chromosome 17. We have genotyped eight previously identified RFLP probes on 50 NF1 families...

X Chromosome–Inactivation Patterns of 1,005 Phenotypically Unaffected Females

Amos-Landgraf, James M., Cottle, Amy, Plenge, Robert M., Friez, Mike, Schwartz, Charles E., Longshore, John, ...

X-chromosome inactivation is widely believed to be random in early female development and to result in a mosaic distribution of cells, approximately half with the paternally derived X chromosome...

Genomic medicine: genetic variation and its impact on the future of health care

Willard, Huntington F, Angrist, Misha, Ginsburg, Geoffrey S

Advances in genome technology and other fruits of the Human Genome Project are playing a growing role in the delivery of health care. With the development of new technologies and opportunities for...

An RNA Polymerase III-Dependent Heterochromatin Barrier at Fission Yeast Centromere 1

Scott, Kristin C., White, Caroline V., Willard, Huntington F.

Heterochromatin formation involves the nucleation and spreading of structural and epigenetic features along the chromatin fiber. Chromatin barriers and associated proteins counteract the spreading of...

Cell cycle–dependent localization of macroH2A in chromatin of the inactive X chromosome

Chadwick, Brian P., Willard, Huntington F.

One of several features acquired by chromatin of the inactive X chromosome (Xi) is enrichment for the core histone H2A variant macroH2A within a distinct nuclear structure referred to as a...

A Novel Chromatin Protein, Distantly Related to Histone H2a, Is Largely Excluded from the Inactive X Chromosome

Chadwick, Brian P., Willard, Huntington F.

Chromatin on the mammalian inactive X chromosome differs in a number of ways from that on the active X. One protein, macroH2A, whose amino terminus is closely related to histone H2A, is enriched on...

Development and application of a phylogenomic toolkit: Resolving the evolutionary history of Madagascar’s lemurs

Horvath, Julie E., Weisrock, David W., Embry, Stephanie L., Fiorentino, Isabella, Balhoff, James P., Kappeler, Peter, ...

Lemurs and the other strepsirrhine primates are of great interest to the primate genomics community due to their phylogenetic placement as the sister lineage to all other primates. Previous attempts...

The Impact of Local Genome Sequence on Defining Heterochromatin Domains

Wheeler, Bayly S., Blau, Jared A., Willard, Huntington F., Scott, Kristin C.

Characterizing how genomic sequence interacts with trans-acting regulatory factors to implement a program of gene expression in eukaryotic organisms is critical to understanding genome function. One...