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Kris Blanchard

Bio: Kris Blanchard is an academic researcher from University of Michigan. The author has contributed to research in topics: Microbiome & Trinucleotide repeat expansion. The author has an hindex of 1, co-authored 1 publications receiving 6756 citations.

Papers
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Journal ArticleDOI
26 Mar 1993-Cell
TL;DR: In this article, the authors used haplotype analysis of linkage disequilibrium to spotlight a small segment of 4p16.3 as the likely location of the defect, which is expanded and unstable on HD chromosomes.

7,224 citations

Posted ContentDOI
30 Oct 2022-medRxiv
TL;DR: The use of prebiotics and probiotics to improve symptoms associated with autism spectrum disorder (ASD) has varied from study to study, indicating the complex and heterogeneous nature of the disorder as discussed by the authors .
Abstract: The use of prebiotics and probiotics to improve symptoms associated with autism spectrum disorder (ASD) has varied from study to study, indicating the complex and heterogeneous nature of the disorder and the behaviors and gastrointestinal symptoms associated with ASD. There is a wide variety in the severity of symptoms and developmental impediments across the population. Gut microbiome studies have also shown unique but varied microbial signatures in ASD. While there have been successes in pre-clinical and clinical trials with prebiotic and probiotic components, the limited population sizes have promising yet inconclusive results. This study addresses this issue by 1) enrolling an ASD cohort of 296 children and adults and comparing their deep DNA metagenomic sequencing of gut microbiomes to that of an age-matched neurotypical cohort and 2) individually formulating a precision synbiotic (probiotic and prebiotic) tailored towards each individual's needs and conducting pre/post evaluations of ASD and GI symptoms and longitudinal whole genome microbiome sequencing. At baseline, there was significantly lower microbiome diversity in the ASD group relative to controls. Microbes, pathways, and gene families significantly differed between the two populations. The ASD microbiome had higher abundances of pathogens, such as Shigella, Klebsiella, Mycobacterium, and Clostridium, but lower abundances of beneficial microbes, including Faecalibacterium. With a 3-month synbiotic supplementation, the microbiome diversity of the 170 ASD participants completing the study increased and became closer to the neurotypical controls. Significant shifts in microbial and pathway abundances were also measured at the second ASD timepoint. In addition to changes in the gut microbiome, there was a significant reduction in gastrointestinal discomfort. There were also improvements in some ASD-related symptoms; however, we cannot exclude that these were potentially due to the open-label nature of the study. Changes in the gut microbiome composition and functional capacity, along with a reduction in gastrointestinal symptoms and potential changes in behavior, highlight the importance of metagenomics, longitudinal studies, and the potential for therapeutic microbial supplementation in ASD.

Cited by
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Journal ArticleDOI
TL;DR: A new algorithm for finding tandem repeats which works without the need to specify either the pattern or pattern size is presented and its ability to detect tandem repeats that have undergone extensive mutational change is demonstrated.
Abstract: A tandem repeat in DNA is two or more contiguous, approximate copies of a pattern of nucleotides. Tandem repeats have been shown to cause human disease, may play a variety of regulatory and evolutionary roles and are important laboratory and analytic tools. Extensive knowledge about pattern size, copy number, mutational history, etc. for tandem repeats has been limited by the inability to easily detect them in genomic sequence data. In this paper, we present a new algorithm for finding tandem repeats which works without the need to specify either the pattern or pattern size. We model tandem repeats by percent identity and frequency of indels between adjacent pattern copies and use statistically based recognition criteria. We demonstrate the algorithm’s speed and its ability to detect tandem repeats that have undergone extensive mutational change by analyzing four sequences: the human frataxin gene, the human β T cell receptor locus sequence and two yeast chromosomes. These sequences range in size from 3 kb up to 700 kb. A World Wide Web server interface at c3.biomath.mssm.edu/trf.html has been established for automated use of the program.

6,577 citations

Journal ArticleDOI
TL;DR: Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins.
Abstract: The distinct protein aggregates that are found in Alzheimer's, Parkinson's, Huntington's and prion diseases seem to cause these disorders. Small intermediates - soluble oligomers - in the aggregation process can confer synaptic dysfunction, whereas large, insoluble deposits might function as reservoirs of the bioactive oligomers. These emerging concepts are exemplified by Alzheimer's disease, in which amyloid beta-protein oligomers adversely affect synaptic structure and plasticity. Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins.

4,499 citations

Journal ArticleDOI
29 Jun 1995-Nature
TL;DR: A minimal cosegregating region containing the AD3 gene is defined, and at least 19 different transcripts encoded within this region corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein.
Abstract: Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3. We have defined a minimal cosegregating region containing the AD3 gene, and isolated at least 19 different transcripts encoded within this region. One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Five different missense mutations have been found that cosegregate with early-onset familial Alzheimer's disease. Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3.

4,110 citations

Journal ArticleDOI
29 Oct 1993-Science
TL;DR: Two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain.
Abstract: There is an increasing amount of experimental evidence that oxidative stress is a causal, or at least an ancillary, factor in the neuropathology of several adult neurodegenerative disorders, as well as in stroke, trauma, and seizures. At the same time, excessive or persistent activation of glutamate-gated ion channels may cause neuronal degeneration in these same conditions. Glutamate and related acidic amino acids are thought to be the major excitatory neurotransmitters in brain and may be utilized by 40 percent of the synapses. Thus, two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain. The broad distribution in brain of the processes regulating oxidative stress and mediating glutamatergic neurotransmission may explain the wide range of disorders in which both have been implicated. Yet differential expression of components of the processes in particular neuronal systems may account for selective neurodegeneration in certain disorders.

3,844 citations

Journal ArticleDOI
07 May 1993-Science
TL;DR: Colorectal tumor DNA was examined for somatic instability at (CA)n repeats on human chromosomes 5q, 15q, 17p, and 18q, and this instability was significantly correlated with the tumor's location in the proximal colon and with increased patient survival and loss of heterozygosity.
Abstract: Colorectal tumor DNA was examined for somatic instability at (CA)n repeats on human chromosomes 5q, 15q, 17p, and 18q. Differences between tumor and normal DNA were detected in 25 of the 90 (28 percent) tumors examined. This instability appeared as either a substantial change in repeat length (often heterogeneous in nature) or a minor change (typically two base pairs). Microsatellite instability was significantly correlated with the tumor's location in the proximal colon (P = 0.003), with increased patient survival (P = 0.02), and, inversely, with loss of heterozygosity for chromosomes 5q, 17p, and 18q. These data suggest that some colorectal cancers may arise through a mechanism that does not necessarily involve loss of heterozygosity.

3,093 citations