Biomedical subjects

R Brdicka

Publications and source records attributed to R Brdicka.

At least 37 records · Page 2Linked to original sources

PubMed1995

[The human genome--chromosome 22].

The 22nd chromosome is known mainly due to chromosome (Philadelphia) which is its derivative-a typical cytogenetic sign of chronic myeloid leukaemia (CML). The molecular genetic finding in these patients is the fused gene which developed by combination of the 3' part of the oncogene ABL from chromosome 9 and 5' part of the gene which developed by combination of the 3' part of the oncogene ABL from chromosome 9 and 5' part of the BCR "gene". The product of the gene retains the original kinase activity (ABL) which is even higher. Detection of BCR/ABL is an important diagnostic aid whic makes it possible to investigate residual diseases in patients after intensive treatment and transplantation of bone marrow and early detection of possible relapses. Among locuses of the 22nd chromosome the author mentions also the locus of the second one of the light immunoglobulin chains-lambda, incl. some of its "related" genes, the group of crystalline locuses (CRYB), the locus of the beta-chain of the GM-CSF receptor, the myoglobin locus (MB) and finally locus NF2 of central neurofibromatosis-bilateral neurinoma of the acoustic nerve.

Chromosome Mapping↗

PubMed1995

[The human genome--chromosome 21].

The 21st chromosome is probably known above all in conjunction with congenital or hereditary trisomy causing Down's syndrome. Its prevalence can be to a certain extent regulated by prevention, planned parenthood and examination during pregnancy. Particularly urgent for contemporary health services, more so in countries with a high mean age, are diseases such as e.g. Alzheimer's dementia, the AD1 locus of which is assumed to be on the 21st chromosome. The locus of the APP precursor of the protein beta-amyloid is suspected, as there in patients from affected families mutational changes were found. That a casual relationship could be involved is suggested also by results obtained in transgenic mice. As to other loci of the 21st chromosome, the author mentions aldo ALS1 for amyotrophic lateral sclerosis and EPMI for progressive myoclonic epilepsy.

Animals↗

PubMed1995

[The human genome--chromosome 18].

The 18th human chromosome is probably known mainly due to patients with Edwards syndrome, children dying usually during the first week of life, the syndrome being due to the presence of three chromosomes 18-trisomy. Some of its loci participate in oncogenesis either as cellular oncogenes (BCL2 in lymphomas), or antioncogenes (DCC--in colorectal carcinomas--Lynch I and Lynch II). It is assumed that some of the causes of maniac depression could be associated with chromosome no. 18.

Chromosomes, Human, Pair 18↗

PubMed1995

[The human genome--chromosome 17].

The submitted account on genes of the 17th chromosome pays attention to autosomal dominant hereditary neurodegenerative diseases which have some characteristics in common-they are relatively frequent, a considerable proportion of the cases is conditioned by new mutations, contributed mainly by male gametes, and they affect mostly the periphery of the nervous system. In addition to the cause of this group of diseases which at present is not yet quite clear, the 17th chromosome is the carrier of the locus the product of which--p53 protein--interferes with oncogenesis. Its effect twofold--the normal product under normal conditions (natural regulation) exerts an antioncogenic action, its shortage or altered quality-(mutations) exert an oncogenic action. Another important locus which is involved in oncogenic processes is locus RARA--the receptor of retinoic acid which participates in the formation of promyelocytic acute leukaemia and locus BRCA1 the pathogenic alleles of which are a dominant predisposition for breast cancer.

Chromosome Mapping↗

PubMed1995

[The human genome--chromosome 16].

Haemoglobinopathies and thalassaemia caused by qualitative and quantitative disorders of the function of the alpha-chain of haemoglobin are associated with chromosome 16 on the short arms of which two of its loci are placed localized mapped. The majority of the human population has four active alpha-chain genes. Reduction of their number to two or less leads to increasing symptoms of their insufficiency manifested as alpha-thalassaemia--complete loss being lethal. On the 16th chromosome is the cause of the dominantly hereditary disease--polycytosis of the kidney so far inaccurately defined at the gene level. The author mentions also the loci of the cholesterylester transfer protein--which participates in the responsibility for hyperlipoproteinaemia and sclerotic changes and loci of haptoglobin chains--one of the serum proteins oldest as regards knowledge of its electrophoretic polymorphism.

Chromosome Mapping↗

PubMed1995

[Autosomal dominant hereditary polycystic kidney disease].

BACKGROUND: Molecular genetics are a fundamental turning point in the approach to autosomal dominant hereditary renal polycystosis of adults (ADPKD). DNA analysis makes diagnosis possible at in any ontogenic period, i.e. also during the prenatal period. The objective of the present study was to test the presymptomatic DNA diagnosis in a major group of patients with ADPKD and the possibility to detect the disease in the initial stage and influence its development by early treatment and advise the patients on parenthood. METHODS AND RESULTS: In 1990-1994 the authors contacted 157 patients with polycystic kidney disease, adult type (ADPKD). 87 families were examined by Southern's RFLP method (gene PKD1, 16p13.3, standard probe 3'HVR and restrictase Pvu II). Of 493 members of these families only 25 (5.1%) refused to be examined. So far 378 examinations were completed, 90 proceed. In 40 of 132 examined subjects with the risk of ADPKD transmission of the gene was proved. Of four examinations of the foetus with the risk of ADPKD twice transmission of the gene was proved and the pregnancy was terminated. In three families with three or more members suffering from ADPKD in some there was not agreement between the result of linkage analysis of DNA and the clinical finding. The authors analyzed whether the cause is recombination or ADKPD conditioned by mutation of gene PKD2 (4p13-23). Linkage analysis remains in ADPKD the basic examination as the sequence of gene PKD1 is not yet completed. Discovery of gene PKD2 the mutations of which condition as many as 15% of all cases of ADPKD has an impact on the evaluation of linkage analysis. The reliability of prediction rises with the number of examined subjects in the family. The examination revealed that patients are willing to have DNA examinations (as many as 98%); despite this the number of examined subjects is only a small fraction of the anticipated 10,000 people in the Czech Republic suffering from ADPKD: CONCLUSIONS: DNA analysis in patients with autosomal dominant polycystic kidney disease is the most important examination for its diagnosis. It makes the diagnosis possible in all stages of ontogenesis, incl. prenatal diagnosis. It is a highly valid parameter when these patients decide on parenthood. It makes early treatment possible which can influence the development of the disease and its complications.

Adult↗

PubMed1995

[The human genome--chromosome 15].

The Prader-Willi syndrome (PWS) with Angelman's syndrome form a pair known above all due to problems of genetic imprinting and uniparental disomy. Both phenomena drew attention to the importance of control of expression of different alleles and their genetic origin. The causes of the two syndromes have not been elucidated unequivocally so far. In case of the PWS, at least, there is the possibility of a gene of the protein carrier of a small nuclear ribonucleic acid described as SNRPN. In case of Marfan's syndrome the responsible gene is the fibrillin gene (FNB1) with the locus on area 15q21. The mentioned gene participates probably also in diseases caused by a change of the vascular wall (aneurysm) and in prolapse of the mitral valves. On the 15th chromosome are several representatives of the family of genes of cytochrome P450 the products of which play a part in the metabolism of exogenous substances, incl. pharmaceutical ones. Their activity is part of the natural sensitivity or resistance to some chemical cancerogens. The postscriptis devoted to the assumed locus of dyslexia DLX1.

Chromosomes, Human, Pair 15↗

PubMed1995

[The human genome--chromosome 14].

In addition to the tandem-like genes of rDNA of ribosomal RNA a special configuration and uncommon implementation is found in loci of receptor chains of T lymphocytes (TCRA, TCRD) and heavy immunoglobulin chain (IGH). In the mature lymphocyte there is, as compared with the germinal genome, its equipment in the above two areas is reduced. Regulators of transcription of these genes may be as a result of chromosomal exchanges which are obviously facilitated by a high local and regional recombination activity, involved in malignant processes. The fourteenth chromosome is the carrier of two genes of heavy myosin chains which by their pathogenic mutations are responsible for hereditary cardiomyopathies. The 14th chromosome is probably also the site of genes controlling the arrangement of internal organs--this is indicated by findings of comparative genetics where the responsible locus is in the close vicinity of locus IGH.

Chromosome Mapping↗

PubMed1995

[The human genome--chromosome 13 with an addendum on the repair system].

The chromosome number 13 which has been investigated least so far is known above all due to two loci: WND-responsible for Wilson's disease caused by impaired copper metabolism and RB1 which as to its effects belongs among so-called anti-oncogenes, i.e. suppressors of oncogenic processes. A special section of the paper deals with DNA - repair systems and their hereditary disorders.

Chromosomes, Human, Pair 13↗

PubMed1995

[The human genome--chromosome 12].

One of the most rewarding examples for teaching hereditary metabolic disorders is classical phenylketonuria (PKU) caused by the deficient function of phenylalanine hydroxylase, the locus of which (PAH) is on the long arm of the twelfth chromosome. The twelfth chromosome has also the locus (VWF, F8VWF) the pathogenic alleles of which cause impaired blood clotting--Willebrand's disease and it is at the same time also the site of the family of keratin genes (KRT) responsible for epidermolysis bullosa simplex and other diseases. The question of the relationship between membrane glucose transmitters--GLUT and diabetes (NIDDM) is the subject of many investigations concerned with these loci.

Chromosome Mapping↗

PubMed1995

[The human genome--chromosome 11].

The eleventh human chromosome is one of the most intensely studied and as regards the number of known genes it holds the third place after chromosomes 1 and X. The best known ones located on it are e.g. loci of the beta-globulin family which are associated with the best known and most widely distributed molecular disease-sickle-cell anaemia and beta-thalassaemia. From knowledge of the causes of these diseases at the genome level so-called DNA diagnostics are derived which can be applied also to the prenatal period. On chromosome 11 are the loci of two complementary groups (C, D) which are extremely sensitive to ionizing radiation--ataxia teleangiectasia, the proinsulin locus the mutations of which, however, are not the cause of common types of diabetes. Development of the urogenital tract as indicated by some of its disorders (WAGR, Denys-Drash syndrome) is controlled by WT genes.

Chromosome Mapping↗

PubMed1995

[The human genome--chromosome 10 and the collagen genes].

In relation to locuses of the 10th chromosome at present the following are in the focus of interest: tumours of endocrine glands, medullary carcinoma of the thyroid gland (MTC) and multiple endocrine neoplasias (MEN). It seems that the unifying basis is the oncogene RET, responsible for the development of Hirschsprung's disease HSCR. The authors mentions also metabolically important locuses for choline acetyltransferase (CHAT), uriporphyrinogen synthase (UROS) and methyl guanine methyltransferase (MGMT). A special paragraph is devoted to a list of collagenous genes COL1-COL18 and diseases associated with them.

Chromosome Mapping↗

PubMed1995

[The human genome--chromosome 9].

Among the contents of chromosome 9 the author mentions locuses for Friedreich's ataxia (FRDA), familial malignant melanoma (MLM), acute hepatic porphyria caused by deficiency of delta-aminolevulinate dehydrogenase (ALAD) and locus XPAC, the defective alleles of which condition disorders of nucleic acid reparative systems. By transcription and translation of the ABL oncogene attached to gene BCR and belonging to the 22nd chromosome a fusion protein with a high kinase activity is formed which is typical for the pathological clone of haematopoietic cells in chronic leukaemia.

Chromosomes, Human, Pair 9↗

PubMed1995

[The human genome--chromosome 8].

From hitherto identified genes located on the 8th human chromosome the author mentions the following: the lipoprotein lipase gene the pathogenic allells of which cause hyperlipoproteinaemia, the ancyrine gene responsible for the development of spherocytosis, the carboanhydrase genes responsible for the development of renal tubular acidosis and the gene of steroid 11-beta-hydroxylase (CYP11B) which is associated with inborn adrenal hyperplasia. The reconstructions and exchanges in which genes of the 8th chromosome participate are frequently found in tumourous processes, in particular in leukaemias type M2 (t8,21). On the 8th chromosome is also the TG locus which in made responsible for the development of non-endemic congenital goitre, and the pharmacogenetically interesting locus of arylamine-N-acetyl transferase.

Chromosomes, Human, Pair 8↗

PubMed1995

[The human genome--chromosome 7].

The seventh chromosome achieved maximum popularity due to locus CFTR the pathological alleles of which cause one of the frequent metabolic hereditary disorders--cystic fibrosis. It is also the site which causes the development of some types of retinitis pigmentosa (RP9, RP10), osteogenesis imperfecta and dominant forms of myotonia congenita. On the long arms there is a complicated multi-segmental gene system of receptors of T-lymphocytes, TCRB, important in cell immunity and it is assumed that it is also the locus of taste perception of phenylthiocarbamide (PTC) is located there.

Chromosomes, Human, Pair 7↗

PubMed1995

[The human genome--chromosome 6].

In addition to the dominating area containing genes MHC-the major histocompatibility complex with a number of other important genes which are between locuses of HLA, the 6th chromosome is the carrier of genes for idiopathic types of epilepsy, haemochromatosis, spinocerebellar ataxia, whereby the latter belongs among diseases caused by expansion of intragenic repetitions. On the 6th chromosome we find also representatives of the family of collagen locuses, COL9A1 and COL11A2, and as clotting factor F13A1. It is assumed that there are also some locuses which control some types of cleft lip and palate.

Chromosomes, Human, Pair 6↗

PubMed1995

[The human genome--chromosome 5].

From the historical aspect the fifth human chromosome is associated with the cri-du-chât syndrome conditioned by deletion of the short arms. The fifth human chromosome is the carrier of genes the pathogenic alleles of which cause one of the most frequent recessive hereditary diseases of child age--spinal muscular atrophy (SMA), the development of tumours of the large bowel and a group of haematological malignant conditions which are part of the so-called 5q-syndrome. It is the carrier of some important gene families-complement, interleukins and growth factors and their receptors; loss of some of them participates in the mentioned 5q-syndrome.

Chromosomes, Human, Pair 5↗

PubMed1995

[The human genome--chromosome 3].

The hitherto little investigated third human chromosome contains genes, the pathogenic alleles of which are responsible for some diseases, in particular retinitis pigmentosa (locus RHO), von Hippel-Lindau syndrome (VHL), epidermolysis bullosa (COL7A1) which is also an example of the situation when different alleles and thus genotypes of the same gene lead to phenotypes which differ so much that they are classified as different diseases. Locuses of the 3rd chromosome participate also in cancerogenesis by the development of the oncogenic genotype as a result of loss of activity or as activated oncogenes. On the third chromosome there is also the locus for alkaptonuria (AKU), a rare metabolic error which is relatively widespread in the north-western part of Slovakia.

Chromosome Mapping↗