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11.
A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region 总被引:10,自引:0,他引:10
Akarsu AN; Turacli ME; Aktan SG; Barsoum-Homsy M; Chevrette L; Sayli BS; Sarfarazi M 《Human molecular genetics》1996,5(8):1199-1203
Primary congenital glaucoma (gene symbol: GLC3) is an ocular disorder that
occurs for 0.01-0.04% of blind people. In the majority of familial cases
reported so far, this condition is inherited as an autosomal recessive
trait. We have recently used a group of 17 GLC3 families with a minimum of
two affected offspring and consanguinity in most of the parental generation
and mapped the first GLC3 locus (GLC3A) to the 2p21 region. Six families
did not show any linkage to the GLC3A locus and thus provided evidence for
genetic heterogeneity of this disorder. A total of eight families unlinked
to the 2p21 region were used to search for the chromosomal location of the
second GLC3 locus. Herein, we describe mapping of a new locus (designated
GLC3B) for primary congenital glaucoma to the short arm of chromosome 1
(1p36.2-36.1) that is situated centromeric to the neuroblastoma and
Charcot-Marie-Tooth type 2A (CMT2A) loci. A total of 17 DNA markers were
genotyped from this region of chromosome 1. Four families showed no
recombination with the two markers D1S2834 and D1S402 with a maximum lod
score of 4.510 and 4.157 respectively. Pairwise and multipoint linkage
analysis and inspection of the haplotypes revealed that the remaining four
families are not linked to this part of chromosome 1, thus providing
further evidence that at least one more locus for the autosomal recessive
form of GLC3 must exist in the genome. Based on the recombination events,
the overall linkage map of this region is: tel-D1S1192-D1S1635-D1S1193 -
(D1S1597/-D1S489/D1S228)- [GLC3B/D1S2834/D1S402] - (D1S1176/D1S507/D1S407)
- D1S2728-(MFAP2/D1S170) - D1S1368 - D1S436- D1S1592-cen.
相似文献
12.
Desai V, Donsante A, Swoboda KJ, Martensen M, Thompson J, Kaler SG. Favorably skewed X‐inactivation accounts for neurological sparing in female carriers of Menkes disease. Classical Menkes disease is an X‐linked recessive neurodegenerative disorder caused by mutations in ATP7A, which is located at Xq13.1‐q21. ATP7A encodes a copper‐transporting P‐type ATPase and plays a critical role in development of the central nervous system. With rare exceptions involving sex chromosome aneuploidy or X‐autosome translocations, female carriers of ATP7A mutations are asymptomatic except for subtle hair and skin abnormalities, although the mechanism for this neurological sparing has not been reported. We studied a three‐generation family in which a severe ATP7A mutation, a 5.5‐kb genomic deletion spanning exons 13 and 14, segregated. The deletion junction fragment was amplified from the proband by long‐range polymerase chain reaction and sequenced to characterize the breakpoints. We screened at‐risk females in the family for this junction fragment and analyzed their X‐inactivation patterns using the human androgen‐receptor (HUMARA) gene methylation assay. We detected the junction fragment in the proband, two obligate heterozygotes, and four of six at‐risk females. Skewed inactivation of the X chromosome harboring the deletion was noted in all female carriers of the deletion (n = 6), whereas random X‐inactivation was observed in all non‐carriers (n = 2). Our results formally document one mechanism for neurological sparing in female carriers of ATP7A mutations. Based on review of X‐inactivation patterns in female carriers of other X‐linked recessive diseases, our findings imply that substantial expression of a mutant ATP7A at the expense of the normal allele could be associated with neurologic symptoms in female carriers of Menkes disease and its allelic variants, occipital horn syndrome, and ATP7A‐related distal motor neuropathy. 相似文献
13.
14.
PurposeTo evaluate the effect of Haishengsu (HSS), a protein extract from Tegillarca granosa, on multidrug-resistance genes mdr1, BCR/ABL and sorcin in transplanted tumors.Material/MethodsMice were inoculated subcutaneously with a drug resistant leukemia cell line K562/ADM. Tumor-bearing animals were divided into control, adriamycin, HSS and combination therapy (adriamycin plus HSS) groups. Flow cytometry was used to detect apoptosis of tumor cells, and RT-PCR was used to evaluate the expression of mdr1, BCR/ABL and sorcin.ResultsThe apoptosis rate in the high (71.8%), medium (72.3%) and low doses HSS group (72.4%) was higher than in control (1.2%, p<0.01), adriamycin (34.4%, p<0.05) or combination therapy group (46.4%, p<0.05). The mean optical density of mdr1, BCR/ABL and sorcin in HSS groups was lower than in control, adriamycin and combination therapy group (p<0.01). The optical density of the three genes in high HSS group was lower than in medium and low HSS group (p<0.01).ConclusionsHaishengsu promotes apoptosis of drug-resistant K562/ADM tumors in mice in a dose-dependent manner. The pro-apoptotic effect of Haishengsu may be related to a reduced expression of multidrug-resistance genes mdr1, BCR/ABL and sorcin. 相似文献
15.
SG Lindquist M Duno M Batbayli A Puschmann H Braendgaard S Mardosiene K Svenstrup LH Pinborg K Vestergaard LE Hjermind J Stokholm BB Andersen P Johannsen JE Nielsen 《Clinical genetics》2013,83(3):279-283
Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene. 相似文献
16.
Evan Wood Mark W Tyndall Calvin Lai Julio SG Montaner Thomas Kerr 《Substance abuse treatment, prevention, and policy》2006,1(1):13-4
North America's first medically supervised safer injecting facility (SIF) recently opened in Vancouver, Canada. One of the
concerns prior to the SIF's opening was that the facility might lead to a migration of drug activity and an increase in drug-related
crime. Therefore, we examined crime rates in the neighborhood where the SIF is located in the year before versus the year
after the SIF opened. No increases were seen with respect to drug trafficking (124 vs. 116) or assaults/robbery (174 vs. 180),
although a decline in vehicle break-ins/vehicle theft was observed (302 vs. 227). The SIF was not associated with increased
drug trafficking or crimes commonly linked to drug use. 相似文献
17.
Mark W Tyndall Evan Wood Ruth Zhang Calvin Lai Julio SG Montaner Thomas Kerr 《Harm reduction journal》2006,3(1):36-5
North America's first government sanctioned medically supervised injection facility (SIF) was opened during September 2003
in Vancouver, Canada. This was in response to a large open public drug scene, high rates of HIV and hepatitis C transmission,
fatal drug overdoses, and poor health outcomes among the city's injection drug users. Between December 2003 and April 2005,
a representative sample of 1,035 SIF participants were enrolled in a prospective cohort that required completing an interviewer-administered
questionnaire and providing a blood sample for HIV testing. HIV infection was detected in 170/1007 (17%) participants and
was associated with Aboriginal ethnicity (adjusted Odds Ratio [aOR], 2.70, 95% Confidence Interval [95% CI], 1.84–3.97), a
history of borrowing used needles/syringes (aOR, 2.0, 95% CI, 1.37–2.93), previous incarceration (aOR, 1.87, 95% CI, 1.11–3.14),
and daily injection cocaine use (aOR, 1.42, 95% CI, 1.00–2.03). The SIF has attracted a large number of marginalized injection
drug users and presents an excellent opportunity to enhance HIV prevention through education, the provision of sterile injecting
equipment, and a supervised environment to self-inject. In addition, the SIF is an important point of contact for HIV positive
individuals who may not be participating in HIV care and treatment. 相似文献
18.
Brandon DL Marshall Thomas Kerr Chris Livingstone Kathy Li Julio SG Montaner Evan Wood 《Harm reduction journal》2008,5(1):35
Aboriginal people experience a disproportionate burden of HIV infection among the adult population in Canada; however, less
is known regarding the prevalence and characteristics of HIV positivity among drug-using and street-involved Aboriginal youth.
We examined HIV seroprevalence and risk factors among a cohort of 529 street-involved youth in Vancouver, Canada. At baseline,
15 (2.8%) were HIV positive, of whom 7 (46.7%) were Aboriginal. Aboriginal ethnicity was a significant correlate of HIV infection
(odds ratio = 2.87, 95%CI: 1.02 – 8.09). Of the HIV positive participants, 2 (28.6%) Aboriginals and 6 (75.0%) non-Aboriginals
reported injection drug use; furthermore, hepatitis C co-infection was significantly less common among Aboriginal participants
(p = 0.041). These findings suggest that factors other than injection drug use may promote HIV transmission among street-involved
Aboriginal youth, and provide further evidence that culturally appropriate and evidence-based interventions for HIV prevention
among Aboriginal young people are urgently required. 相似文献
19.
Evidence for endogenous formation of tobacco-specific nitrosamines in rats treated with tobacco alkaloids and sodium nitrite 总被引:2,自引:0,他引:2
Carcinogenic tobacco-specific nitrosamines are present in tobacco products
and are believed to play a significant role in human cancers associated
with tobacco use. Additional amounts of tobacco-specific nitrosamines could
be formed endogenously. We tested this hypothesis by treating rats with
nicotine and sodium nitrite and analyzing their urine. Initially, we
treated groups of rats with (S)-nicotine (60 micromol/kg) and NaNO2 (180
micromol/kg), (S)-nicotine alone, NaNO2 alone or
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 12 nmol/kg) by gavage
twice daily for 4 days. We collected urine and analyzed for two metabolites
of NNK; 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanol and its glucuronide.
We did not detect these metabolites in the urine of rats treated with
nicotine alone or nicotine plus NaNO2, indicating that endogenous
conversion of nicotine to NNK did not occur. However, the urine did contain
N'- nitrosonornicotine (NNN), N'-nitrosoanabasine (NAB) and N'-
nitrosoanatabine (NAT). Analysis of the (S)-nicotine used in this
experiment demonstrated that it contained trace amounts of nornicotine,
anabasine and anatabine. In a second experiment, we used an identical
protocol to compare the endogenous nitrosation of this (S)-nicotine with
that of synthetic (R,S)-nicotine, which did not contain detectable amounts
of nornicotine, anabasine or anatabine. NNN (0.53 x 10(-3)% of nicotine
dose), NAB (0.68%) and NAT (2.1%) were detected in the urine of the rats
treated with the (S)-nicotine and NaNO2. NNN (0.47 x 10(- 3)% of dose), but
not NAB or NAT, was present in the urine of the rats treated with synthetic
(R,S)-nicotine and NaNO2. NNN probably formed via nitrosation of
metabolically formed nornicotine. These results demonstrate for the first
time that endogenous formation of tobacco- specific nitrosamines occurs in
rats treated with tobacco alkaloids and NaNO2. The potential significance
of the results with respect to nitrosamine formation in people who use
tobacco products or nicotine replacement therapy is discussed.
相似文献
20.