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RESEARCH PROGRAM
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Research Units
Similar research programs:
- 1 - Hypoxia-induced angiogenetic genes: susceptibility factors to Amyotrophic Lateral Sclerosis ?
- 2 - BETA-AMYLOID PRODUCTION AND CLEARANCE IN PATIENTS WITH ALZHEIMER DISEASE AND MILD COGNITIVE IMPAIRMENT: IN VITRO STUDIES AND EX VIVO MARKERS
- 3 - Control mechanisms of erythropoiesis and congenital and familial polycythemias: role of oxygen-sensing pathways
- 4 - A high-throughput integrative biology study for the genetic dissection of IgA Nephropathy
- 5 - Metabolic and molecular bases of Down syndrome
- 6 - Studies on the molecular mechanisms of abnormal parathyroid proliferation and function, and identification and clinical use of molecular markers of sporadic and familial parathyroid cancer. New insights on the prevalence of skeletal, neuropsychological and metabolic manifestations of primary hyperparathyroidism, their relationship with calcium sensing receptor polymorphisms and course after parathyroidectomy.
- 7 - Physiology and pathophysiology of erythropoiesis: molecular characterization by advanced high throughput approaches.
- 8 - Study of aldosterone genomic effects in cellular and in vivo models.
- 9 - Hereditary spastic paraplegias: a genetic, functional and clinical study
- 10 - From the study of global regulation of gene expression to the study of virulence in Mycobacterium tuberculosis
Scientific and education field classification
- Field: Scienze biologiche
International Patent Classification
- CHEMISTRY; METALLURGY
- BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- MEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICRO-ORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
Bibliografia
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Keywords
AGC1, AUTISM, MACROCEPHALY, MICROARRAY, PEPTIDURIA, RECONSTITUTION INTO LIPOSOMES, SEROTONIN, SLC25A12, MITOCHONDRIAL TRANSPORTERSBiochemical and genetic studies of autistic disorder
Abstract
Autism is a severe neuropsychiatric disorder, whose incidence has apparently risen during the last decade from 2-5 to 15-20/10,000 children. This disease is today recognized as the consequence of biochemical alterations, deranging prenatal neurodevelopmental processes. It represents the neuropsychiatric disorder displaying the heaviest genetic component, with heritability estimates greater than 90% according to twin studies.To study this complex disease, we have set up and coordinate since 1997 a long-standing network of nine clinical groups and four laboratories, which have collected DNA, plasma and urines from 273 simplex and 27 multiplex families, including 328 primary autistic patients, and our recruitment is continuing to reach its final target of 400 families. Since specific subgroups of autistic patients are characterized by “biochemical markers of disease” or “endophenotypes”, namely hyperserotoninemia, oligopeptiduria, and macrocephaly, we already have assessed serotonin blood levels, and urinary peptide excretion rates in 152, and 180 autistic patients, and in 325 and 400 first-degree relatives, respectively. Fronto-occipital cranial circumference has been recorded in 247 patients and 54 unaffected siblings. These data are particularly important because “markers” are more closely related to underlying genetic variants and biochemical pathogenetic mechanisms than the complex, polymorphic and variable clinical symptomatology of autism.
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Principal Investigator
Antonio Maria Persico Università "Campus Bio-Medico" ROMAResearch Objectives
The objective of the present Research Program is to study the biochemical and neurobiological alterations underlying autistic disorder. In order to reduce the degree of clinical and etiological heterogeneity, while maximizing the probability to identify biochemical and genetic factors involved in the pathogenesis of the disease, we shall employ three different and complementary strategies: [a] the characterization and study of biological markers of disease or “endophenotypes”, i.e. biochemical or morphological parameters characterizing specific subgroups of patients, yielding phenotypes closer to the biochemical and genetic levels than the complex and variable behavioral symptomatology; [b] parallel biochemical and genetic studies of molecules potentially involved in autism pathogenesis and/or in the abovementioned endophenotypes; [c] an hypothesis-free search for autism susceptibility genes, based upon a genome-wide transcriptional assessment performed using microarray technologies.In reference to the first strategy, the best-characterized endophenotypes in autism research consist of hyperserotoninemia, oligopeptiduria and macrocephaly (i.e., fronto-occipital cranial circumference >97th percentile). Each endophenotype characterizes approximately 20-40% of the patients (see sect. 2.2). We shall thus employ a large sample of patients and first-degree relatives already largely characterized in reference to these three parameters, and we shall study six >>>



