Oswald Theodore Avery (October 21, 1877–1955) was a Canadian-born American physician and medical researcher. The major part of his career was spent at the Rockefeller Institute Hospital in New York City. Avery was one of the first molecular biologists and was a pioneer in immunochemistry, but he is best known for his discovery in 1944 with his co-workers Colin MacLeod and Maclyn McCarty, that DNA is the material of which genes and chromosomes are made.

Early life and career

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Oswald Theodore Avery was born on 21 October 1877 in Halifax, Nova Scotia, the second of three sons of Elizabeth Crowdy and Joseph Francis Avery. A Baptist minister in England, Joseph Avery and his wife emigrated to Canada in 1873. Established as a well-respected pastor in Halifax, he moved his family to New York City in 1887, where he was appointed pastor of the Mariner's Temple Baptist mission church on the lower East Side. Each member of the family participated in the church: Elizabeth was involved with charities and the newsletter while young "Ossie" and his oldest brother, Ernest, often played clarinet on the church steps to attract new attendees. Ernest died early in 1892 at the age of eighteen, probably from tuberculosis. Several months later, Reverend Avery also died. Following their deaths, the then fifteen-year old Oswald assumed the paternal role for his youngest brother, Roy, a part he would also play some years later to his cousin, Minnie Wandell, whom Roy often affectionately referred to as "little sister."

After attending the New York Male Grammar School, Avery went to the Colgate Academy and then Colgate University, where he excelled in literature, public speaking, and debate. While at Colgate, he was a classmate of Harry Emerson Fosdick, who would become one of the most notable clergymen in America; it is likely that when Avery started at Colgate he also intended to enter the ministry. Avery received a BA in the humanities in 1900. For reasons that are not clear, and despite the absence of any scientific background, after college Avery chose a career in medicine and entered the College of Physicians and Surgeons in New York. He received his medical degree in 1904.

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Human Molecular Genetics - current issue

Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy
Geier, C., Gehmlich, K., Ehler, E., Hassfeld, S., Perrot, A., Hayess, K., Cardim, N., Wenzel, K., Erdmann, B., Krackhardt, F., Posch, M. G., Bublak, A., Nagele, H., Scheffold, T., Dietz, R., Chien, K. R., Spuler, S., Furst, D. O., Nurnberg, P., Ozcelik, C. Tue, 26 Aug 2008 00:00:00 -0000
Hypertrophic cardiomyopathy (HCM) is a frequent genetic cardiac disease and the most common cause of sudden cardiac death in young individuals. Most of the currently known HCM disease genes encode sarcomeric proteins. Previous studies have shown an association between CSRP3 missense mutations and either dilated cardiomyopathy (DCM) or HCM, but all these studies were unable to provide comprehensive genetic evidence for a causative role of CSRP3 mutations. We used linkage analysis and identified a CSRP3 missense mutation in a large German family affected by HCM. We confirmed CSRP3 as an HCM disease gene. Furthermore, CSRP3 missense mutations segregating with HCM were identified in four other families. We used a newly designed monoclonal antibody to show that muscle LIM protein (MLP), the protein encoded by CSRP3, is mainly a cytosolic component of cardiomyocytes and not tightly anchored to sarcomeric structures. Our functional data from both in vitro and in vivo analyses suggest that at least one of MLP’s mutated forms seems to be destabilized in the heart of HCM patients harbouring a CSRP3 missense mutation. We also present evidence for mild skeletal muscle disease in affected persons. Our results support the view that HCM is not exclusively a sarcomeric disease and also suggest that impaired mechano-sensory stress signalling might be involved in the pathogenesis of HCM.
PTHR1 mutations associated with Ollier disease result in receptor loss of function
Couvineau, A., Wouters, V., Bertrand, G., Rouyer, C., Gerard, B., Boon, L. M., Grandchamp, B., Vikkula, M., Silve, C. Tue, 26 Aug 2008 00:00:00 -0000
PTHR1-signaling pathway is critical for the regulation of endochondral ossification. Thus, abnormalities in genes belonging to this pathway could potentially participate in the pathogenesis of Ollier disease/Maffucci syndrome, two developmental disorders defined by the presence of multiple enchondromas. In agreement, a functionally deleterious mutation in PTHR1 (p.R150C) was identified in enchondromas from two of six unrelated patients with enchondromatosis. However, neither the p.R150C mutation (26 tumors) nor any other mutation in the PTHR1 gene (11 patients) could be identified in another study. To further define the role of PTHR1-signaling pathway in Ollier disease and Maffucci syndrome, we analyzed the coding sequences of four genes (PTHR1, IHH, PTHrP and GNAS1) in leucocyte and/or tumor DNA from 61 and 23 patients affected with Ollier disease or Maffucci syndrome, respectively. We identified three previously undescribed missense mutations in PTHR1 in patients with Ollier disease at the heterozygous state. Two mutations (p.G121E, p.A122T) were present only in enchondromas, and one (p.R255H) in both enchondroma and leukocyte DNA. Assessment of receptor function demonstrated that these three mutations impair PTHR1 function by reducing either the affinity of the receptor for PTH or the receptor expression at the cell surface. These mutations were not found in DNA from 222 controls. Including our data, PTHR1 functionally deleterious mutations have now been identified in five out 31 enchondromas from Ollier patients. These findings provide further support for the idea that heterozygous mutations in PTHR1 that impair receptor function participate in the pathogenesis of Ollier disease in some patients.
Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions
Yehezkel, S., Segev, Y., Viegas-Pequignot, E., Skorecki, K., Selig, S. Tue, 26 Aug 2008 00:00:00 -0000
Telomeres and adjacent subtelomeric regions are packaged as heterochromatin in many organisms. The heterochromatic features include DNA methylation, histones H3-Lys9 (Lysine 9) and H4-Lys20 (Lysine 20) methylation and heterochromatin protein1 alpha binding. Subtelomeric DNA is hypomethylated in human sperm and ova, and these regions are subjected to de novo methylation during development. In mice this activity is carried out by DNA methyltransferase 3b (Dnmt3b). Mutations in DNMT3B in humans lead to the autosomal-recessive ICF (immunodeficiency, centromeric region instability, facial anomalies) syndrome. Here we show that, in addition to several satellite and non-satellite repeats, the subtelomeric regions in lymphoblastoid and fibroblast cells of ICF patients are also hypomethylated to similar levels as in sperm. Furthermore, the telomeres are abnormally short in both the telomerase-positive and -negative cells, and many chromosome ends lack detectable telomere fluorescence in situ hybridization signals from either one or both sister-chromatids. In contrast to Dnmt3a/b–/– mouse embryonic stem cells, increased telomere sister-chromatid exchange was not observed in ICF cells. Hypomethylation of subtelomeric regions was associated in the ICF cells with advanced telomere replication timing and elevated levels of transcripts emanating from telomeric regions, known as TERRA (telomeric-repeat-containing RNA) or TelRNA. The current findings provide a mechanistic explanation for the abnormal telomeric phenotype observed in ICF syndrome and highlights the link between TERRA/TelRNA and structural telomeric integrity.

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