Ken Livak - Academia.edu (original) (raw)

Papers by Ken Livak

Gynecologic Oncology, 2005

Nucleosides, Nucleotides & Nucleic Acids, Jun 1, 1999

Automated synthesis of molecular beacons using 4-(4-dimethylamino phenylazo) benzoic acid (dabcyl... more Automated synthesis of molecular beacons using 4-(4-dimethylamino phenylazo) benzoic acid (dabcyl) support and phosphoramidite is described.

American Journal of Human Genetics, Sep 1, 1994

ABSTRACT The dopamine D4 receptor (DRD4) is a candidate gene for schizophrenia because the dopami... more ABSTRACT The dopamine D4 receptor (DRD4) is a candidate gene for schizophrenia because the dopaminergic system has been implicated in this neuropsychiatric disorder. Several research groups have reported an association between allelic variants at DRD4 and schizophrenia, while others have been unable to replicate that finding. Knowledge of the appropriate gene frequencies in the underlying populations may resolve these inconsistencies. We have determined the frequencies of 8 different alleles of the 48 bp imperfect tandem repeat of exon 3 at the DRD4 locus in samples from 33 populations around the world. The frequencies vary considerably in the different populations with the most common allele ranging from 16% to 95%. Frequencies and Fst values will be presented for the 3 most common alleles (4-, 7-, and 2- repeat) by continental groupings, but the individual populations vary significantly around the averages. The populations averaged 4.3 alleles (range 2 to 7).

Cellular reprogramming through manipulation of defined factors holds great promise for large-scal... more Cellular reprogramming through manipulation of defined factors holds great promise for large-scale production of cell types needed for use in therapy, as well as for expanding our understanding of the general principles of gene regulation. MYOD-mediated myogenic reprogramming, which converts many cell types into contractile myotubes, remains one of the best characterized model system for direct conversion by defined factors. However, why MYOD can efficiently convert some cell types into myotubes but not others remains poorly understood. Here, we analyze MYOD-mediated reprogramming of human fibroblasts at pseudotemporal resolution using single-cell RNA-Seq. Successfully reprogrammed cells navigate a trajectory with two branches that correspond to two barriers to reprogramming, with cells that select incorrect branches terminating at aberrant or incomplete reprogramming outcomes. Differential analysis of the major branch points alongside alignment of the successful reprogramming path to a primary myoblast trajectory revealed Insulin and BMP signaling as crucial molecular determinants of an individual cell's reprogramming outcome, that when appropriately modulated, increased efficiency more than five-fold. Our single-cell analysis reveals that MYOD is sufficient to reprogram cells only when the extracellular milieu is favorable, supporting MYOD with upstream signaling pathways that drive normal myogenesis in development. .

Regular and Young Investigator Award Abstracts, Nov 1, 2022

Regular and Young Investigator Award Abstracts

We describe an extension of the fluoro genic PCR 5 ′ -nuclease assay, or “Taq Man ™ ” assay. Sequ... more We describe an extension of the fluoro genic PCR 5 ′ -nuclease assay, or “Taq Man ™ ” assay. Sequence-specific probe s consisted of a novel nonfluorescent quench er, nitrothiazole blue (NTB), at the 3 ′ term i nus and six different reporter dyes at the 5 ′ terminus. The six reporters were 6-FAM , dR110, dR6G, dTMR, dROX and JAZ dyes . The seventh color was from aluminum ph thalocyanine tetrasulfonate and was utilized as a “passive reference” to calibrate concen tration variations. Our test system was a se t of three single-nucleotide polymorphism s (SNPs). Each SNP system consisted of two primers and two sequence-specific probes , each labeled with a different reporter dy e and NTB. Following PCR, the reactions wer e diluted with water and measured in a m i crocuvette on a luminescence spectromete r in synchronous scanning mode. In thi s method, both the excitation and emission wavelengths were scanned, with a fixed wavelength difference (Δ λ ) between excita tion and emission wavel...

Nucleosides and Nucleotides, 1999

Nucleic Acids Research, 1998

A fast cleaving non-nucleosidic tetramethylrhodamine dye-labeled support has been developed for a... more A fast cleaving non-nucleosidic tetramethylrhodamine dye-labeled support has been developed for automated synthesis of double dye-labeled oligodeoxyribonucleotides in high yield. A mixture (1:1:2) of t-butylamine:methanol:water is used for cleavage and deprotection of dye-labeled oligodeoxyribonucleotides without any degradation or modification of dyes and nucleobases. The cleavage rate of oligodeoxyribonucleotides is significantly increased by using a diglycolate ester linkage instead of the commonly used succinate linkage. These double dye-labeled probes are used in PCR for real time detection of a specific PCR product. Using a 5′-exonuclease assay, detected on the ABI PRISM 7700 Sequence Detection System, there was no distinguishable difference in performance of probes synthesized using the dyelabeled support compared with traditional postsynthetic attachment of rhodamine.

Differentiation and Development, 1978

American Journal of Medical Genetics, 1993

The discovery of a functional polymrphism within the dopamine D4 receptor gene (DRD4) has not onl... more The discovery of a functional polymrphism within the dopamine D4 receptor gene (DRD4) has not only strengthened the hypotheses implicating DRD4 in the etiology of neuropyschiatic disorders, but also provided a genetic marker for testing these hypotheses. The possibility of the dopamine D4 receptor as a candidate gene for schizophrenia was investigated in a large Swedish kindred segregating for schizophrenia. Linkage to schizophrenia was tested by linkage analyses of 6 polymorphic markers (at 4 loci) in chromosome 11p15.5 including the dopamine D4 receptor (DRD4) and the tyrosine hydroxylase (TH) loci. Schizophrenia was excluded from close linkage to the DRD4 locus using two of the polymorphisms located within the dopamine D4 receptor gene. The first DRD4 polymorphism consists of variation in the number of a 48 bp imperfect direct repeat in the third exon; the second consists of a variable number of repeated G nucleotides in the first intron. In addition, some of the individuals homo...

The American Journal of Human Genetics, 2000

There has been great interest in the prospects of using single-nucleotide polymorphisms (SNPs) in... more There has been great interest in the prospects of using single-nucleotide polymorphisms (SNPs) in the search for complex disease genes, and several initiatives devoted to the identification and mapping of SNPs throughout the human genome are currently underway. However, actual data investigating the use of SNPs for identification of complex disease genes are scarce. To begin to look at issues surrounding the use of SNPs in complex disease studies, we have initiated a collaborative SNP mapping study around APOE, the well-established susceptibility gene for late-onset Alzheimer disease (AD). Sixty SNPs in a 1.5-Mb region surrounding APOE were genotyped in samples of unrelated cases of AD, in controls, and in families with AD. Standard tests were conducted to look for association of SNP alleles with AD, in cases and controls. We also used family-based association analyses, including recently developed methods to look for haplotype association. Evidence of association () was identified for 7 of 13 P р .05 SNPs, including the APOE-4 polymorphism, spanning 40 kb on either side of APOE. As expected, very strong evidence for association with AD was seen for the APOE-4 polymorphism, as well as for two other SNPs that lie !16 kb from APOE. Haplotype analysis using family data increased significance over that seen in single-locus tests for some of the markers, and, for these data, improved localization of the gene. Our results demonstrate that associations can be detected at SNPs near a complex disease gene. We found that a high density of markers will be necessary in order to have a good chance of including SNPs with detectable levels of allelic association with the disease mutation, and statistical analysis based on haplotypes can provide additional information with respect to tests of significance and fine localization of complex disease genes.

Gene Quantification, 1996

Page 113. Quantitative PCR Technology Lincoln McBride, Ken Livak, Mike Lucero. ... Jeff Lucas, Ke... more Page 113. Quantitative PCR Technology Lincoln McBride, Ken Livak, Mike Lucero. ... Jeff Lucas, Kevin Bodner, Robert Grossman, Bashar Mullah. Charles Connell, LindaLee, and Mark Oldham Introduction Higuchi et al.(1992. ...