scholarly journals Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

10.3791/58907 ◽  
2019 ◽  
Author(s):  
Edward G Jones ◽  
Andrew P Landstrom
Keyword(s):  
Genetic Variation ◽  
Amino Acid ◽  
Acid Level ◽  
Noise Analysis ◽  
Amino Acid Level ◽  
Signal To Noise

scholarly journals Amino acid–level signal-to-noise analysis of incidentally identified variants in genes associated with long QT syndrome during pediatric whole exome sequencing reflects background genetic noise

Heart Rhythm ◽  
2018 ◽  
Vol 15 (7) ◽  
pp. 1042-1050 ◽  
Author(s):  
Andrew P. Landstrom ◽  
Ernesto Fernandez ◽  
Jill A. Rosenfeld ◽  
Yaping Yang ◽  
Andrew L. Dailey-Schwartz ◽  
...  
Keyword(s):  
Amino Acid ◽  
Exome Sequencing ◽  
Long Qt Syndrome ◽  
Acid Level ◽  
Noise Analysis ◽  
Amino Acid Level ◽  
Signal To Noise ◽  
Long Qt ◽  
Whole Exome ◽  
Qt Syndrome

scholarly journals Amino Acid-level Signal-to-Noise Analysis Aids in Pathogenicity Prediction of Incidentally-identified TTN -Encoded Titin Truncating Variants

2020 ◽  
Author(s):  
Patrick S. Connell ◽  
Amy M. Berkman ◽  
BriAnna M. Souder ◽  
Elisa J. Pirozzi ◽  
Julia J. Lovin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Level ◽  
Noise Analysis ◽  
Amino Acid Level ◽  
Signal To Noise ◽  
Variants Of Unknown Significance ◽  
Diagnostic Interpretation ◽  
Clinical Exome Sequencing ◽  
Pathogenicity Prediction ◽  
Unknown Significance

Background - TTN , the largest gene in the human body, encodes titin (TTN), a protein that plays key structural, developmental, and regulatory roles in skeletal and cardiac muscle. Variants in TTN , particularly truncating variants (TTNtvs), have been implicated in the pathogenicity of cardiomyopathy (CM). Despite this link, there is also a high burden of TTNtvs in the ostensibly healthy general population. This complicates the diagnostic interpretation of incidentally identified TTNtvs which are of increasing abundance given expanding clinical exome sequencing (ES). Methods - Incidentally identified TTNtvs were obtained from a large referral database of clinical ES (Baylor Genetics) and compared to rare population variants from gnomAD and CM-associated variants from cohort studies in the literature. A subset of TTNtv-positive children evaluated for cardiomyopathy at Texas Children's Hospital (TCH) were retrospectively reviewed for clinical features of cardiomyopathy. Amino acid-level signal-to-noise analysis (S:N) was performed. Results - Pathologic hotspots were identified within the A-band and N-terminal I-band that closely correlated with regions of high percent spliced in (PSI) of exons. Incidental TTNtvs and population TTNtvs did not localize to these regions. Variants were re-classified based on current ACMG criteria with incorporation of S:N analysis among TCH cases. Those re-classified as likely pathogenic or pathogenic were more likely to have evidence of CM on echocardiography than those re-classified as variants of unknown significance. Conclusions - Incidentally found TTNtvs are common among clinical ES referrals. Pathologic hotspots within the A-band of TTN may be informative in determining variant pathogenicity when incorporated into current ACMG guidelines.

scholarly journals Halogenation of glycopeptide antibiotics occurs at the amino acid level during non-ribosomal peptide synthesis

2017 ◽  
Vol 8 (9) ◽  
pp. 5992-6004 ◽  
Author(s):  
Tiia Kittilä ◽  
Claudia Kittel ◽  
Julien Tailhades ◽  
Diane Butz ◽  
Melanie Schoppet ◽  
...  
Keyword(s):  
Amino Acid ◽  
Peptide Synthesis ◽  
Acid Level ◽  
Amino Acid Level ◽  
Antibiotic Biosynthesis ◽  
Carrier Protein ◽  
Glycopeptide Antibiotics ◽  
Glycopeptide Antibiotic ◽  
Protein Substrates

Halogenase enzymes involved in glycopeptide antibiotic biosynthesis accept aminoacyl-carrier protein substrates.

Plastein reaction as a method for enhancing the sulfur-containing amino acid level of soybean protein

1971 ◽  
Vol 19 (6) ◽  
pp. 1151-1154 ◽  
Author(s):  
Michiko. Yamashita ◽  
Soichi. Arai ◽  
Shun-Jen. Tsai ◽  
Masao. Fujimaki
Keyword(s):  
Amino Acid ◽  
Acid Level ◽  
Soybean Protein ◽  
Amino Acid Level ◽  
Plastein Reaction ◽  
Sulfur Containing

Influence of Amino Acid Level in the Diet upon Amino Acid Oxidation by the Rat

1972 ◽  
Vol 102 (1) ◽  
pp. 27-35 ◽  
Author(s):  
I. M. Brookes ◽  
F. N. Owens ◽  
U. S. Garrigus
Keyword(s):  
Amino Acid ◽  
Acid Level ◽  
Amino Acid Level ◽  
Acid Oxidation ◽  
Amino Acid Oxidation

Source and function of urinary ammonia in the alligator

1959 ◽  
Vol 197 (4) ◽  
pp. 873-879 ◽  
Author(s):  
Roland A. Coulson ◽  
Thomas Hernandez
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Acid Level ◽  
Amino Acid Level ◽  
Plasma Amino Acid ◽  
Plasma Amino Acids ◽  
Renal Reabsorption ◽  
And Function ◽  
Phosphate Solutions

The rate of renal deamination of 18 amino acids was determined by injecting them into alligators and measuring the ammonia excreted. Not only did glycine, alanine, glutamine and leucine account for nearly half of the plasma amino acids, they were also deaminated more rapidly than any of the others. In view of this it was concluded that these four amino acids are the natural precursors of urinary NH3 in the alligator. Increased NH3 and CO2 excretion following glycine injections resulted in increased renal reabsorption of Na and Cl when NaCl was injected and increased Na reabsorption when NaHCO3 or Na phosphate solutions were injected. The fact that excess NH4HCO3 excretion enhances salt reabsorption independent of plasma pH makes it probable that the excretion of N is the chief function of the ammonia mechanism and that salt conservation is incidental. Insulin decreased the plasma amino acid level and drastically reduced the NH3 excretion. With the decrease in ammonia, NaCl and NaHCO3 were excreted in increased amounts.

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