Wyniki wyszukiwania - Biblioteka Nauki

1

Mutations in type I collagen genes resulting in osteogenesis imperfecta in humans.

100%

Gajko-Galicka A.

Acta Biochimica Polonica

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2002

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tom 49

|

nr 2

433-441

EN

Osteogenesis imperfecta (OI), commonly known as "brittle bone disease", is a dominant autosomal disorder characterized by bone fragility and abnormalities of connective tissue. Biochemical and molecular genetic studies have shown that the vast majority of affected individuals have mutations in either the COL1A1 or COL1A2 genes that encode the chains of type I procollagen. OI is associated with a wide spectrum of phenotypes varying from mild to severe and lethal conditions. The mild forms are usually caused by mutations which inactivate one allele of COL1A1 gene and result in a reduced amount of normal type I collagen, while the severe and lethal forms result from dominant negative mutations in COL1A1 or COL1A2 which produce structural defects in the collagen molecule. The most common mutations are substitutions of glycine residues, which are crucial to formation and function of the collagen triple helix, by larger amino acids. Although type I collagen is the major structural protein of both bone and skin, the mutations in type I collagen genes cause a bone disease. Some reports showed that the mutant collagen can be expressed differently in bone and in skin. Since most mutations identified in OI are dominant negative, the gene therapy requires a fundamentally different approach from that used for genetic-recessive disorders. The antisense therapy, by reducing the expression of mutant genes, is able to change a structural mutation into a null mutation, and thus convert severe forms of the disease into mild OI type I.

2

The effect of Arg209 to Lys mutation in mouse thymidylate synthase.

100%

Cieśla J. , Gołos B. , Wałajtys-Rode E. , Jagielska E. , Płucienniczak A. , Rode W.

Acta Biochimica Polonica

|

2002

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tom 49

|

nr 3

651-658

EN

Mouse thymidylate synthase R209K (a mutation corresponding to R218K in Lactobacillus casei), overexpressed in thymidylate synthase-deficient Escherichia coli strain, was poorly soluble and with only feeble enzyme activity. The mutated protein, incubated with FdUMP and N5,10-methylenetetrahydrofolate, did not form a complex stable under conditions of SDS/polyacrylamide gel electrophoresis. The reaction catalyzed by the R209K enzyme (studied in a crude extract), compared to that catalyzed by purified wild-type recombinant mouse thymidylate synthase, showed the Km value for dUMP 571-fold higher and Vmax value over 50-fold (assuming that the mutated enzyme constituted 20% of total crude extract protein) lower. Thus the ratios kcat, R209K/kcat, 'wild' and (kcat, R209K/Km, R209KdUMP)/( kcat, 'wild'/Km, 'wild'dUMP) were 0.019 and 0.000032, respectively, documenting that mouse thymidylate synthase R209, similar to the corresponding L. casei R218, is essential for both dUMP binding and enzyme reaction.

3

In vitro expression analysis of R68G and R68S mutations in phenylalanine hydroxylase gene.

100%

Żekanowski C. , Perez B. , Desviat L. R. , Wiszniewski W. , Ugarte M.

Acta Biochimica Polonica

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2000

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tom 47

|

nr 2

365-369

EN

Phenylketonuria (PKU), an autosomal recessive disorder caused be a deficiency of hepatic phenylalanine hydroxylase (PAH), is clinically very heterogeneous. At the molecular level, more than 400 mutations in the PAH gene are known to date, which in different genotype combinations could account for biochemical and clinical variability of symptoms. In vitro expression studies on R68G and R68S mutations causing mild phenylketonuria are presented.

4

Report on the D32 CCR5 variant in the Sudanese Shagia tribe

100%

Kempińska-Podhorodecka A. , Knap O. , Parczewski M. , Bińczak-Kuleta A. , Parafiniuk M.

Anthropological Review

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2008

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tom 71

|

nr 1

71-76

EN

The focus on small isolated populations provides important insights into the factors affecting the distribution of inheritable traits. Here, we present a report on the distribution of the CCR5 Δ32 mutation in the so far unstudied innate Sudanese population of Shagia people. The genetic material (buccal swabs) was collected from 125 individuals living in three African villages, Abu Haraz, Shibabit and El Higiena. The DNA was extracted, the polymorphic site PCR-amplified with a pair of specific primers flanking the Δ32 CCR5 mutation and reaction products electrophoretically separated in agarose gel. In the Abu Haraz and Shibabit villages, all investigated individuals were found to be homozygous for the wildtype of the receptor, while in El Higiena village one wt/D32 homozygote was identified with the remaining individuals homozygous for non-mutated CCR5. The frequency for the Δ32 CCR5 allele was 0,4%, with Δ32/wt genotype frequency of 0,8%. This is the first report on the presence of the Δ32 CCR5 allele not only in the genetically isolated Shagia tribe but also in the region of the Sudan.

PL

W trakcie ekspedycji naukowej w rejon obejmujący obszar IV katarakty na Nilu, między miastami Karima i Abu Hamad, w lutym 2005 r., zabezpieczono materiał genetyczny w postaci wymazów z nabłonka jamy ustnej od 125 osób z plemienia Shagia. Po przeprowadzeniu izolacji, DNA poddano amplifikacji metodą PCR przy użyciu pary specyficznych (flankujących) primerów. Produkty reakcji zostały rozdzielone elektroforetycznie na żelu agarozowym, w celu ujawnienia i identyfikacji ewentualnie istniejącej mutacji Δ;32 CCR5. Zidentyfikowano jedną heterozygotę wt/D32, podczas gdy pozostali przebadani osobnicy byli homozygotyczni w zakresie niezmutowanego CCR5 (tab. 1). Oporność na zakażenie wirusem HIV jest związana ze zmniejszeniem ilości funkcjonalnego receptora CCR-5 na powierzchni komórek, przez co wnikanie wirusa HIV odbywa się ze znacznie mniejszą efektywnością. Częstość występowania badanych polimorfizmów jest znacząco mniejsza na kontynencie afrykańskim niż w Europie (tab. 2). Homozygotyczność w zakresie allelu Δ;32 niesie za sobą niemal całkowitą oporność na zakażenie wirusem. Zaprezentowane badania są unikatowe w skali afrykańskiej, szczególnie dla wybranej zamkniętej populacji i pozwalają uzyskać istotny wgląd w zmienność genetyczną tamtejszej ludności. Interesujący jest sam fakt odnalezienia omawianej mutacji wśród ludu Shagia. Może to być związane z wcześniej prowadzonym, koczowniczym trybem życia oraz ewentualną domieszką genów europejskich.

5

APC gene in mutated in endometrial cancer of women

100%

Miturski R. , Burnouf D. , Nothisen M. , Tomaszewski J. , Jakowicki J. , Fuchs R.

Cellular and Molecular Biology Letters

|

1998

|

tom 03

|

nr 2

6

Mitochondrial diseases

88%

Paulouskaya V.

Edukacja Biologiczna i Środowiskowa

|

2014

|

nr 1

12-18

EN

Mitochondria are found in every nucleated cell of the human body. The major function of these cell compartments is energy production. Mitochondria are the only orgenalles of the human cells that have their own genetic material – mitochondrial DNA, that is because of their bacterial ancestry. Mutations in the mtDNA as well as in the nuclear genome cause mitochondrial diseases, the symptoms of which are very diverse. Mitochondrial dysfunction is a common phenomenon of many disorders, also of neurodegenarative diseases.

7

Biochemical characterization of a catalase from Vibrio vulnificus, a pathogen that causes gastroenteritis

88%

Pei J. , Wang H. , Wu L. , Xia S. , Xu C. , Zheng B. , Li T. , Jiang Y.

Acta Biochimica Polonica

|

2017

|

tom 64

|

nr 3

543-549

EN

Vibrio vulnificus is a virulent human pathogen causing gastroenteritis and possibly life threatening septicemia in patients. Most V. vulnificus are catalase positive and can deactivate peroxides, thus allowing them to survive within the host. In the study presented here, a catalase from V. vulnificus (CAT-Vv) was purified to homogeneity after expression in Escherichia coli. The kinetics and function of CAT-Vv were examined. CAT-Vv catalyzed the reduction of H2O2 at an optimal pH of 7.5 and temperature of 35°C. The Vmax and Km values were 65.8±1.2 U/mg and 10.5±0.7 mM for H2O2, respectively. Mutational analysis suggests that amino acids involved in heme binding play a key role in the catalysis. Quantitative reverse transcription-PCR revealed that in V. vulnificus, transcription of CAT-Vv was upregulated by low salinity, heat, and oxidative stresses. This research gives new clues to help inhibit the growth of, and infection by V. vulnificus.

8

Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III

88%

Augusciak-Duma A. , Witecka J. , Sieron A. , Janeczko M. , Pietrzyk J. , Ochman K. , Galicka A. , Borszewska-Kornacka M. , Pilch J. , Jakubowska-Pietkiewicz E.

Acta Biochimica Polonica

|

2018

|

tom 65

|

nr 1

79-86

EN

Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families.

9

A novel homozygous mutation in the WNK1/HSN2 gene causing hereditary sensory neuropathy type 2

88%

Potulska-Chromik A. , Kabzińska D. , Lipowska M. , Kostera-Pruszczyk A. , Kochański A.

Acta Biochimica Polonica

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2012

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tom 59

|

nr 3

413-415

EN

Hereditary sensory and autonomic neuropathy type 2 is a rare disorder caused by recessive mutations in the WNK1/HSN2 gene located on chromosome 12p13.33. Phenotype of the patients is characterized by severe sensory loss affecting all sensory modalities. We report a novel homozygous Lys179fsX182 (HSN2); Lys965fsX968 (WNK1/HSN2) mutation causing an early childhood onset hereditary sensory and autonomic neuropathy type 2, with acromutilations in upper and lower limbs, and autonomic dysfunction. To the best of our knowledge this is the first genetically proven case of hereditary sensory and autonomic neuropathy type 2 originating from East Europe.

10

Reversion of argE3 ochre strain Escherichia coli AB1157 as a tool for studying the stationary-phase [adaptive] mutations

88%

Nowosielska A. , Grzesiuk E.

Acta Biochimica Polonica

|

2000

|

tom 47

|

nr 2

EN

Adaptive (starvation-associated) mutations occur in non-dividing cells and allow growth under the selective conditions imposed. We developed a new method for the determination of adaptive mutations in Escherichia coli. The system involves reversion to prototrophy of the argE3OC mutation and was tested on AB1157 strains mutated in the mutT and/or mutY genes. The bacteria that mutated adaptively grow into colonies on minimal medium plates devoid of arginine (starvation conditions) when incubated longer than 4 days. Using the replica plating method we solved the problem of discrimination between growth-dependent and adaptive argE3Arg+ revertants. Phenotype analysis and susceptibility of the Arg+ revertants to a set of T4 phage mutants create an additional possibility to draw a distinction between these two types of Arg+ revertants.

11

A new dominant mutant in mink [ Mustela vison Schreber ]

88%

Trapezov O. V. , Tikhomirov I. B. , Tikhomirova V. V.

Zeszyty Naukowe. Przegląd Hodowlany

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1996

|

tom 27

12

Analysis of unstable DNA sequence in FRM1 gene in Polish families with fragile X syndrome

88%

Milewski M. , Zygulska M. , Bal J. , Deelen W. H. , Obersztyn E. , Bocian E. , Halley D. J. J. , Horst J. , Mazurczak T.

Acta Biochimica Polonica

|

1996

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tom 43

|

nr 2

13

The frequency of mutations in Exon 11 of the CF gene in Polish cystic fibrosis patients

88%

Bal J. , Mazurczak T. , Reiss J.

Acta Biochimica Polonica

|

1992

|

tom 39

|

nr 3

EN

Results of mutation analysis in exon II of the CF gene have been presented. Using the SSCI' technique 18 mutations (of four different types) were detected in cystic fibrosis patients of Polish origin. Thus, we were able to detect in exon 11 about 10% of all CF mutations occuring in the affected population examined.

14

Ovarian cystadenoma as a characteristics feature of families with hereditary ovarian cancers unassociated with BRCA1 and BRCA2 mutations

88%

Menkiszak J. , Brzosko M. , Gorski B. , Flicinski J. , Jakubowska A. , Zebielowicz D. , Gronwald J. , Huzarski T. , Byrski T. , Teresinski L. , Chosia M. , Rzepka-Gorska I. , Lubinski J.

Journal of Applied Genetics

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2004

|

tom 45

|

nr 2

15

Analysis of unstable DNA sequence in FMR1 gene in Polish families with fragile X syndrom

88%

Milewski M. , Zygulska M. , Bal J. , Deelen W. H. , Obersztyn E. , Bocian E. , Halley D. J. J. , Horst J. , Mazurczak T.

Acta Biochimica Polonica

|

1996

|

tom 43

|

nr 2

EN

The unstable DNA sequence in the FMR1 gene was analyzed in 85 individuals from Polish families with fragile X syndrome in order to characterize mutations responsible for the disease in Poland. In all affected individuals classified on the basis of clinical features and expression of the fragile site at X(q27.3) a large expansion of the unstable sequence (full mutation) was detected. About 5% (2 of 43) of individuals with full mutation did not express the fragile site. Among normal alleles, ranging in size from 20 to 41 CGG repeats, allele with 29 repeats was the most frequent (37%). Transmission of premutated and fully mutated alleles to the offspring was always associated with size increase. No change in repeat number was found when normal alleles were transmitted.

16

TP53 and mutations in human cancer

88%

Szymanska K. , Hainaut P.

Acta Biochimica Polonica

|

2003

|

tom 50

|

nr 1

EN

TP53 is the most frequently mutated gene in human cancer, with a predominance of missense mutations scattered over 200 codons. In many cancers, specific mutation patterns can be identified, which are shaped by site-specific mutagenesis and by biological selection. In tobacco-related cancers (lung, head and neck), organ-specific patterns are observed, with many mutations compatible with the ones experimentally induced by tobacco carcinogens. In several other cancers, such as squamous cell carcinoma of the oesophagus or hepatocellular carcinoma (HCC), mutation patterns show geographic variations between regions of high and low incidence, suggesting a role for region-specific risk factors. HCC from high-incidence regions showing also a high prevalence of a specific Ser-249 TP53 mutation is one of the most striking examples of a mutagen fingerprint. All such assessments are useful to generate clues on the mutagenic mechanisms involved in human cancer. Moreover, it has been shown that DNA retrieved from plasma can be successfully used for detection of TP53 mutations, which gives hope for earlier more accurate detection of human cancers.

17

Screening for mutations in the GJB3 gene in Brazilian patients with nonsyndromic deafness

88%

Alexandrino F. , Oliveira C. A. , Reis F. C. , Maciel-Guerra A. T. , Sartorato E. L.

Journal of Applied Genetics

|

2004

|

tom 45

|

nr 2

18

TP53 and mutations in human cancer.

75%

Szymańska K. , Hainaut P.

Acta Biochimica Polonica

|

2003

|

tom 50

|

nr 1

231-238

EN

TP53 is the most frequently mutated gene in human cancer, with a predominance of missense mutations scattered over 200 codons. In many cancers, specific mutation patterns can be identified, which are shaped by site-specific mutagenesis and by biological selection. In tobacco-related cancers (lung, head and neck), organ-specific patterns are observed, with many mutations compatible with the ones experimentally induced by tobacco carcinogens. In several other cancers, such as squamous cell carcinoma of the oesophagus or hepatocellular carcinoma (HCC), mutation patterns show geographic variations between regions of high and low incidence, suggesting a role for region-specific risk factors. HCC from high-incidence regions showing also a high prevalence of a specific Ser-249 TP53 mutation is one of the most striking examples of a mutagen fingerprint. All such assessments are useful to generate clues on the mutagenic mechanisms involved in human cancer. Moreover, it has been shown that DNA retrieved from plasma can be successfully used for detection of TP53 mutations, which gives hope for earlier more accurate detection of human cancers.

19

Loss of heterozygosity at BRCA1-2 loci in hereditary and sporadic ovarian cancers

75%

Brozek I. , Ochman K. , Debniak J. , Morzuch L. , Ratajska M. , Stepnowska M. , Stukan M. , Emerich J. , Limon J.

Journal of Applied Genetics

|

2009

|

tom 50

|

nr 4

379-384

EN

Loss of heterozygosity at BRCA 1/2 loci in breast and ovarian tumors is a suggested risk factor for germline BRCA1/2 mutation status. We evaluated the presence of losses of selected microsatellite markers localized on chromosomes 17 and 13q in hereditary and sporadic ovarian tumors. 151 consecutive primary ovarian tumors (including 21 with BRCA1/2 mutations and 130 without the mutations) were screened for loss of heterozygosity at loci on chromosomes 17 and 13q. Losses of heterozygosity of at least one microsatellite marker localized on chromosomes 17 and 13q were revealed in 123 (81.5%) and 104 (68.9%) tumors, respectively. Losses of all informative markers on chromosomes 17 and 13 occurred in 30 (19.9%) and 31 (20.5%) tumors, respectively. There was no difference in the frequency of losses at BRCA1 intragenic markers (D17S855 and D17S1323) between BRACA1-positive and BRCA1-negative patients. The frequency of losses on chromosome 17 was higher in high-grade than in low-grade carcinomas. Loss of heterozygosity on chromosomes 17 and 13q is a frequent phenomenon in both hereditary and sporadic ovarian cancers. The frequency of losses at BRCAl intragenic markers in the ovarian tumor tissue is not strongly related to the presence of BRCAl germline mutations.

20

Andersen-Tawil syndrome (ATS) - case report and literature review

75%

Olszewska K. , Blaszczak J. , Mielnik-Blaszczak M.

Journal of Pre-Clinical and Clinical Research

|

2014

|

tom 08

|

nr 2

EN

Andersen-Tawil Syndrome (ATS) is a rare genetic disorder inherited in an autosomal dominant pattern caused by mutations in the KCNJ2 gene encoding Kir2.1 protein forming potassium ion channel, leading to disruption of cardiac and skeletal muscle repolarisation. Clinical symptoms include periodic paralysis, ventricular arrhythmia associated with QT prolongation and typical skeletal and facial dysmorphic features. The aim of the study was to present characteristic features of the rare Andersen-Tawil syndrome (ATS) within the face and oral cavity of a 9-year-old boy. The patient was diagnosed with Andersen-Tawil syndrome (OMIM#170390) at the age of 8 due to the positive family history, typical dysmorphic features, and the presence of mutation in the KCNJ2 gene confirmed by genetic testing. Typical manifestations of ATS were diagnosed: cardiac arrhythmia, short stature, scoliosis and clinodactyly. Clinical examination revealed typical facial dysmorphic features of ATS: broad forehead, triangular shape of the face, hypertelorism, microstomia, low-set ears, and mandibular retrognathism. Intraoral examination revealed: high-arched palate, crowding in the dental arches, hypomineralisation of enamel and high incidence of dental caries. Dental age assessment by Demirijan pointed to delayed development of permanent dentition. Cephalometric analysis revealed skeletal class II with high angle vertical jaws relation. Diagnosis of ATS requires high index of suspicion because of a great variability in the clinical manifestation of the syndrome. The subtle nature of the dysmorphic features often delays the diagnosis of this syndrome, and its potentially lethal cardiac arrhythmia remaining undetected.