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1

Pendred syndrome in a large consanguineous Brazilian family caused by a homozygous mutation in the SLC26A4 gene.  

PubMed

Pendred Syndrome (PS) is an autossomal recessive disorder characterized by sensorineural deafness, goiter and iodide organification defect. The hearing loss is associated with inner ear abnormalities, ranging from an isolated enlarged vestibular aqueduct (EVA) to a typical coclear dysplasia. Mutations in the gene that encodes pendrin (SLC26A4), a chloride/iodide transporter, have been shown to be associated with PS. We describe the clinical and molecular characteristics of a large consanguineous family harboring a mutation in the SLC26A4 gene. The proband was a 26-year-old deaf Brazilian woman who presented a bulky multinodular goiter and hypothyroidism since puberty. Five other siblings were deaf: one brother had a similar phenotype, three siblings also had goiters but normal thyroid function tests, and one brother had only a subtle thyroid enlargement. Other 4 siblings had no thyroid or hearing disorder. Parents were first degree cousins and had normal hearing. The mother was healthy, except for subclinical hypothyroidism; the father was deceased. A perchlorate test in the proband showed a discharge of 21% of the incorporated iodide 2h after the administration of 1g of KClO4. Audiological examinations showed profound hearing loss in all deaf subjects; CT and MRI of the temporal bones showed EVA in all of them. Genomic DNA was isolated from whole blood, from the 6 affected and 4 unaffected siblings, the mother and control. The coding region of the PDS gene (exons 2-21), including exon/intron boundaries, were amplified by PCR and sequenced. A single base-pair (T) deletion at position 1197 of exon 10 was detected in homozygous state in the 6 deaf siblings. The mother and 2 unaffected siblings were heterozygous for this mutation, which has been described by Everett et al. The 1197delT mutation is predicted to result in a frameshift and a truncated protein. The existence of PS phenocopies and intrafamilial phenotypic variability are well documented. The definite diagnosis requires molecular analysis. Our study illustrates the value and challenges of mutational analysis in selected patients with PS. PMID:19169484

Lofrano-Porto, Adriana; Barra, Gustavo B; Nascimento, Paula P; Costa, Patrícia G G; Garcia, Erica C; Vaz, Rodrigo F; Batista, Ana R T; Freitas, Ana C R de; Cherulli, Bruno L B; Bahmad, Fayez; Figueiredo, Larissa G; Neves, Francisco A R; Casulari, Luiz Augusto

2008-11-01

2

A novel mutation disrupting the cytoplasmic domain of CRB1 in a large consanguineous family of Palestinian origin affected with Leber congenital amaurosis.  

PubMed

Leber congenital amaurosis (LCA) is a genetically heterogeneous autosomal recessive condition responsible for congenital blindness or greatly impaired vision since birth. Eight LCA loci have been mapped, but only six out of eight genes have been hitherto identified. A genome-wide screen for homozygosity was conducted in a large consanguineous family originating from Palestine, for which no mutation was found in any of the six known LCA genes and that excluded the LCA3 and LCA5 loci. Evidence for homozygosity, however, was found in all affected patients of the family on chromosome 1q31, a region in which the human homologue of the Drosophila melanogaster crumbs gene (CRB1) has been mapped. Consequently, we proposed a hypothesis that the disease-causing mutation in this family might lie in an unexplored region of this LCA gene. As a matter of fact, while no mutation was found in any of the 11 CRB1 exons originally reported, we identified a 10-bp (del 4121-4130) deletion segregating with the disease in a later reported 12th exon lying in the 3' end of the gene. Interestingly, this deletion disrupts an amino acid sequence that was shown to be crucial for the function of the protein in the Drosophila counterpart (CRB). PMID:12567265

Gerber, Sylvie; Perrault, Isabelle; Hanein, Sylvain; Shalev, Stavit; Zlotogora, Joel; Barbet, Fabienne; Ducroq, Dominique; Dufier, Jean; Munnich, Arnold; Rozet, Jean; Kaplan, Josseline

2002-12-01

3

A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family.  

PubMed

Asymmetric cell division is essential for normal human brain development. Mutations in several genes encoding centrosomal proteins that participate in accurate cell division have been reported to cause autosomal recessive primary microcephaly (MCPH). By homozygosity mapping including three affected individuals from a consanguineous MCPH family from Pakistan, we delineated a critical region of 18.53 Mb on Chromosome 1p21.3-1p13.1. This region contains the gene encoding HsSAS-6, a centrosomal protein primordial for seeding the formation of new centrioles during the cell cycle. Both next-generation and Sanger sequencing revealed a homozygous c.185T>C missense mutation in the HsSAS-6 gene, resulting in a p.Ile62Thr substitution within a highly conserved region of the PISA domain of HsSAS-6. This variant is neither present in any single-nucleotide polymorphism or exome sequencing databases nor in a Pakistani control cohort. Experiments in tissue culture cells revealed that the Ile62Thr mutant of HsSAS-6 is substantially less efficient than the wild-type protein in sustaining centriole formation. Together, our findings demonstrate a dramatic impact of the mutation p.Ile62Thr on HsSAS-6 function and add this component to the list of genes mutated in primary microcephaly. PMID:24951542

Khan, Muzammil A; Rupp, Verena M; Orpinell, Meritxell; Hussain, Muhammad S; Altmüller, Janine; Steinmetz, Michel O; Enzinger, Christian; Thiele, Holger; Höhne, Wolfgang; Nürnberg, Gudrun; Baig, Shahid M; Ansar, Muhammad; Nürnberg, Peter; Vincent, John B; Speicher, Michael R; Gönczy, Pierre; Windpassinger, Christian

2014-11-15

4

A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome).  

PubMed

Hirschsprung disease, mental retardation, microcephaly, and specific craniofacial dysmorphism were observed in three children from a large, consanguineous, Moroccan family. A fourth child showed similar clinical features, with the exception of Hirschsprung disease. The association of these abnormalities in these children represents the Goldberg-Shprintzen syndrome (OMIM 235730). Mutation scanning of genes potentially involved in Hirschsprung disease, RET, GDNF, EDN3, and EDNRB, showed a sequence variant, Ser305Asn, in exon 4 of the EDNRB gene in the index patient of this family. The Ser305Asn substitution present in two of the four patients and four healthy relatives and absent in one of the remaining two patients illustrates the difficulties in interpreting the presence of mutations in families with Hirschsprung disease. It is unlikely that the EDNRB variant contributes to the phenotype. This consanguineous family might be useful for the identification of a Goldberg-Shprintzen locus. PMID:10874640

Brooks, A S; Breuning, M H; Osinga, J; vd Smagt, J J; Catsman, C E; Buys, C H; Meijers, C; Hofstra, R M

1999-06-01

5

A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome)  

PubMed Central

Hirschsprung disease, mental retardation, microcephaly, and specific craniofacial dysmorphism were observed in three children from a large, consanguineous, Moroccan family. A fourth child showed similar clinical features, with the exception of Hirschsprung disease. The association of these abnormalities in these children represents the Goldberg-Shprintzen syndrome (OMIM 235730).?  Mutation scanning of genes potentially involved in Hirschsprung disease, RET, GDNF, EDN3, and EDNRB, showed a sequence variant, Ser305Asn, in exon 4 of the EDNRB gene in the index patient of this family. The Ser305Asn substitution present in two of the four patients and four healthy relatives and absent in one of the remaining two patients illustrates the difficulties in interpreting the presence of mutations in families with Hirschsprung disease. It is unlikely that the EDNRB variant contributes to the phenotype. This consanguineous family might be useful for the identification of a Goldberg-Shprintzen locus.???Keywords: Hirschsprung disease; microcephaly; mental retardation; EDNRB variant PMID:10874640

Brooks, A.; Breuning, M.; Osinga, J.; Smagt, J.; Catsman, C.; Buys, C.; Meijers, C.; Hofstra, R.

1999-01-01

6

Mutations in patients with osteogenesis imperfecta from consanguineous Indian families.  

PubMed

Osteogenesis imperfecta (OI) is a spectrum of genetic disorders with decreased bone density and bone fragility. Most of the cases of OI are inherited in autosomal dominant fashion with mutations in COL1A1 or COL1A2 genes. Over last few years, twelve genes for autosomal recessive OI have been identified. In this study we have evaluated seven patients with OI from consanguineous Indian families. Homozygosity mapping using SNP microarray was done and selected candidate genes were sequenced. Candidate genes were identified in four out of seven patients studied. Four mutations, namely; a homozygous non-sense (p.Q178*) and a deletion (p.F277del) mutations in SERPINF1 gene, a missense mutation (p.M101K) in PPIB gene and a nonsense mutation (p.E45*) in CRTAP gene were identified. In three patients for whom the regions of homozygosity did not reveal any known autosomal recessive OI genes, exome sequencing was performed and we identified a known missense mutation (p.G1012S) in COL1A2 gene in one of the patients. As WNT1 gene was not properly covered in exome sequencing in one patient, the gene was sequenced and a homozygous in-frame deletion of four amino acids (p.Phe176_Leu179del) was identified. In one of the three cases the exome sequencing did not reveal a mutation in any known OI genes, suggesting the possibility of mutations in an unidentified gene. The phenotypes of all the cases are described. This work proves the power of homozygosity mapping followed by candidate gene sequencing approach for clinical application in consanguineous families. PMID:25450603

Stephen, Joshi; Girisha, Katta Mohan; Dalal, Ashwin; Shukla, Anju; Shah, Hitesh; Srivastava, Priyanka; Kornak, Uwe; Phadke, Shubha R

2015-01-01

7

Mowat-Wilson syndrome in a Moroccan consanguineous family  

PubMed Central

Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum. This disorder is sporadic and is caused by heterozygous mutations or deletions of the ZFHX1B gene located in the 2q22 region. We report here the first Moroccan patient, born to consanguineous parents, with Mowat-Wilson syndrome, due to a de novo, unreported mutation of the ZFHX1B gene. PMID:21957361

Ratbi, Ilham; Elalaoui, Chafai Siham; Dastot-Le, Moal Florence; Goossens, Michel; Giurgea, Irina; Sefiani, Abdelaziz

2007-01-01

8

Identification of a homozygous splice site mutation in the dynein axonemal light chain 4 gene on 22q13.1 in a large consanguineous family from Pakistan with congenital mirror movement disorder.  

PubMed

Mirror movements (MRMV) are involuntary movements on one side of the body that mirror voluntary movements on the opposite side. Congenital mirror movement disorder is a rare, typically autosomal-dominant disorder, although it has been suspected that some sporadic cases may be due to recessive inheritance. Using a linkage analysis and a candidate gene approach, two genes have been implicated in congenital MRMV disorder to date: DCC on 18q21.2 (MRMV1), which encodes a netrin receptor, and RAD51 on 15q15.1 (MRMV2), which is involved in the maintenance of genomic integrity. Here, we describe a large consanguineous Pakistani family with 11 cases of congenital MRMV disorder reported across five generations, with autosomal recessive inheritance likely. Sanger sequencing of DCC and RAD51 did not identify a mutation. We then employed microarray genotyping and autozygosity mapping to identify a shared region of homozygosity-by-descent among the affected individuals. We identified a large autozygous region of ~3.3 Mb on chromosome 22q13.1 (Chr22:36605976-39904648). We used Sanger sequencing to exclude several candidate genes within this region, including DMC1 and NPTXR. Whole exome sequencing was employed, and identified a splice site mutation in the dynein axonemal light chain 4 gene, DNAL4. This splice site change leads to skipping of exon 3, and omission of 28 amino acids from DNAL4 protein. Linkage analysis using Simwalk2 gives a maximum Lod score of 6.197 at this locus. Whether or how DNAL4 function may relate to the function of DCC or RAD51 is not known. Also, there is no suggestion of primary ciliary dyskinesis, situs inversus, or defective sperm in affected family members, which might be anticipated given a putative role for DNAL4 in axonemal-based dynein complexes. We suggest that DNAL4 plays a role in the cytoplasmic dynein complex for netrin-1-directed retrograde transport, and in commissural neurons of the corpus callosum in particular. This, in turn, could lead to faulty cross-brain wiring, resulting in MRMV. PMID:25098561

Ahmed, Iltaf; Mittal, Kirti; Sheikh, Taimoor I; Vasli, Nasim; Rafiq, Muhammad Arshad; Mikhailov, Anna; Ohadi, Mehrnaz; Mahmood, Huda; Rouleau, Guy A; Bhatti, Attya; Ayub, Muhammad; Srour, Myriam; John, Peter; Vincent, John B

2014-11-01

9

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family  

PubMed Central

Background Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. Methods We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. Results A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. Conclusion The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family. PMID:23151256

2012-01-01

10

Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity  

PubMed Central

Non-specific intellectual disability of autosomal recessive inheritance (NS-ARID) represents an important fraction of severe cognitive dysfunction disorders. To date, only 10 genes have been identified, and further 24 linked-ARID loci have been reported, as well as others with suggestive linkage. To discover novel genes causing NS-ARID, we undertook genome-wide homozygosity mapping in 64 consanguineous multiplex families of Syrian descent. A total of 11 families revealed unique, significantly linked loci at 4q26-4q28 (MRT17), 6q12-q15 (MRT18), 18p11 (MRT19), 16p12-q12 (MRT20), 11p15 (MRT21), 11p13-q14 (MRT23), 6p12 (MRT24), 12q13-q15 (MRT25), 14q11-q12 (MRT26), 15q23-q26 (MRT27), and 6q26-q27 (MRT28), respectively. Loci ranged between 1.2 and 45.6?Mb in length. One family showed linkage to chromosome 8q24.3, and we identified a mutation in TRAPPC9. Our study further highlights the extreme heterogeneity of NS-ARID, and suggests that no major disease gene is to be expected, at least in this study group. Systematic analysis of large numbers of affected families, as presented here, will help discovering the genetic causes of ID. PMID:21629298

Abou Jamra, R; Wohlfart, Sigrun; Zweier, Markus; Uebe, Steffen; Priebe, Lutz; Ekici, Arif; Giesebrecht, Susanne; Abboud, Ahmad; Al Khateeb, Mohammed Ayman; Fakher, Mahmoud; Hamdan, Saber; Ismael, Amina; Muhammad, Safia; Nöthen, Markus M; Schumacher, Johannes; Reis, André

2011-01-01

11

Sporadic case of X-chromosomal Alport syndrome in a consanguineous family.  

PubMed

Alport syndrome (AS) is a genetic disorder of basement membranes caused by mutations in type IV collagen genes that is characterized by chronic hematuria and progressive nephropathy leading to renal failure. The main extrarenal features include sensorineural hearing loss and ocular lesions. The mode of inheritance is X-linked dominant in about 80%-85% of the affected families, whereas autosomal transmission is rarely encountered. We report a male patient originating from a healthy consanguineous Lebanese family who presented with an unusual association of obstructive uropathy and AS. Hematuria and proteinuria were initially attributed to a suspected poststreptococcal glomerulonephritis (GN) and high-grade subpelvic ureteral stenosis. Persistence of symptoms after medical treatment of poststreptococcal GN and surgical correction of obstructive uropathy finally led to renal biopsy. The observed ultrastructural changes of the glomerular basement membrane were typical for AS. Molecular genetic studies revealed a previously undescribed de novo mutation in the COL4A5 gene, excluding maternal heterozygotic carrier status. This case report emphasizes the importance of hereditary nephritis in the differential diagnosis of chronic hematuria, and demonstrates the value of molecular studies for genetic counselling in AS. PMID:10955921

Ermisch, B; Gross, O; Netzer, K O; Weber, M; Brandis, M; Zimmerhackl, L B

2000-08-01

12

A novel homozygous ISPD gene mutation causing phenotype variability in a consanguineous family.  

PubMed

Within the group of muscular dystrophies, dystroglycanopathies represent an important subgroup of recessively inherited disorders. Their severity varies from the relatively mild forms of adult-onset limb-girdle muscular dystrophy (LGMD), to the severe congenital muscular dystrophies (CMD) with cerebral and ocular involvement. We describe 2 consanguineous children of Pakistani origin, carrying a new homozygous missense mutation c.367G>A (p.Gly123Arg) in the ISPD gene. Mutations in this gene have been recently reported as a common cause of congenital and limb-girdle muscular dystrophy. Patient 1 is an 8-year-old female with an intermediate phenotype between CMD and early LGMD; patient 2 is a 20-month-old male and second cousin of patient 1, showing a CMD phenotype. Cognitive development, brain MRI, eye examination, electrocardiogram and echocardiogram were normal in both patients. To our knowledge, this is the first report on the co-occurrence of both a CMD/early LGMD intermediate phenotype and a CMD within the same family carrying a homozygous ISPD mutation. PMID:25444434

Baranello, Giovanni; Saredi, Simona; Sansanelli, Serena; Savadori, Paolo; Canioni, Eleonora; Chiapparini, Luisa; Balestri, Paolo; Malandrini, Alessandro; Arnoldi, Maria Teresa; Pantaleoni, Chiara; Morandi, Lucia; Mora, Marina

2015-01-01

13

Lack of KIF21A mutations in congenital fibrosis of the extraocular muscles type I patients from consanguineous Saudi Arabian families  

PubMed Central

Purpose Congenital fibrosis of the extraocular muscles type I (CFEOM1), the most common CFEOM worldwide, is characterized by bilateral ptotic hypotropia, an inability to supraduct above the horizontal midline, horizontal strabismus (typically exotropia), and ophthalmoplegia with abnormal synkinesis. This distinct non-syndromic phenotype is considered autosomal dominant and is virtually always from heterozygous missense mutations in kinesin family member 21A (KIF21A). However, there are occasional KIF21A-negative cases, opening the possibility for a recessive cause. The objective of this study is to explore this possibility by assessing CFEOM1 patients exclusively from consanguineous families, who are the most likely to have recessive cause for their phenotype if a recessive cause exists. Methods Ophthalmic examination and candidate gene direct sequencing (KIF21A, paired-like homeobox 2A [PHOX2A], tubulin beta-3 [TUBB3]) of CFEOM1 patients from consanguineous families referred for counseling from 2005 to 2010. Results All 5 probands had classic CFEOM1 as defined above. Three had siblings with CFEOM. None of the probands had mutations in KIF21A, PHOX2A, or TUBB3. Conclusions The lack of KIF21A mutations in CFEOM1 patients exclusively from consanguineous families, most of whom had siblings with CFEOM, is strong evidence for a recessive form of CFEOM1. Further studies of such families will hopefully uncover the specific locus(loci). PMID:21264235

Shinwari, Jameela; Omar, Aisha; Al-Sharif, Latifa; Khalil, Dania S.; Alanazi, Mohammed; Al-Amri, Abdullah; Al Tassan, Nada

2011-01-01

14

Accelerating Novel Candidate Gene Discovery in Neurogenetic Disorders via Whole-Exome Sequencing of Prescreened Multiplex Consanguineous Families.  

PubMed

Our knowledge of disease genes in neurological disorders is incomplete. With the aim of closing this gap, we performed whole-exome sequencing on 143 multiplex consanguineous families in whom known disease genes had been excluded by autozygosity mapping and candidate gene analysis. This prescreening step led to the identification of 69 recessive genes not previously associated with disease, of which 33 are here described (SPDL1, TUBA3E, INO80, NID1, TSEN15, DMBX1, CLHC1, C12orf4, WDR93, ST7, MATN4, SEC24D, PCDHB4, PTPN23, TAF6, TBCK, FAM177A1, KIAA1109, MTSS1L, XIRP1, KCTD3, CHAF1B, ARV1, ISCA2, PTRH2, GEMIN4, MYOCD, PDPR, DPH1, NUP107, TMEM92, EPB41L4A, and FAM120AOS). We also encountered instances in which the phenotype departed significantly from the established clinical presentation of a known disease gene. Overall, a likely causal mutation was identified in >73% of our cases. This study contributes to the global effort toward a full compendium of disease genes affecting brain function. PMID:25558065

Alazami, Anas M; Patel, Nisha; Shamseldin, Hanan E; Anazi, Shamsa; Al-Dosari, Mohammed S; Alzahrani, Fatema; Hijazi, Hadia; Alshammari, Muneera; Aldahmesh, Mohammed A; Salih, Mustafa A; Faqeih, Eissa; Alhashem, Amal; Bashiri, Fahad A; Al-Owain, Mohammed; Kentab, Amal Y; Sogaty, Sameera; Al Tala, Saeed; Temsah, Mohamad-Hani; Tulbah, Maha; Aljelaify, Rasha F; Alshahwan, Saad A; Seidahmed, Mohammed Zain; Alhadid, Adnan A; Aldhalaan, Hesham; AlQallaf, Fatema; Kurdi, Wesam; Alfadhel, Majid; Babay, Zainab; Alsogheer, Mohammad; Kaya, Namik; Al-Hassnan, Zuhair N; Abdel-Salam, Ghada M H; Al-Sannaa, Nouriya; Al Mutairi, Fuad; El Khashab, Heba Y; Bohlega, Saeed; Jia, Xiaofei; Nguyen, Henry C; Hammami, Rakad; Adly, Nouran; Mohamed, Jawahir Y; Abdulwahab, Firdous; Ibrahim, Niema; Naim, Ewa A; Al-Younes, Banan; Meyer, Brian F; Hashem, Mais; Shaheen, Ranad; Xiong, Yong; Abouelhoda, Mohamed; Aldeeri, Abdulrahman A; Monies, Dorota M; Alkuraya, Fowzan S

2015-01-13

15

Coexistence of mal de Meleda and congenital cataract in a consanguineous Tunisian family: two case reports  

PubMed Central

Introduction Mal de Meleda is a rare form of palmoplantar keratoderma, with autosomal recessive transmission. It is characterized by diffuse erythema and hyperkeratosis of the palms and soles. Recently, mutations in the ARS (component B) gene (ARS, MIM: 606119) on chromosome 8q24.3 have been identified in families with this disorder. Congenital cataract is a visual disease that may interfere with sharp imaging of the retina. Mutations in the heat-shock transcription factor 4 gene (HSF4; MIM: 602438) may result in both autosomal dominant and autosomal recessive congenital cataracts. Case presentation A Tunisian family with two female siblings aged 45 and 30 years, presented with a clinical association of mal de Meleda and congenital cataract. The two patients exhibited diffuse palmoplantar keratodermas. One of them presented with a total posterior subcapsular cataract and had a best corrected visual acuity at 1/20 in the left eye and with the right eye was only able to count fingers at a distance of one foot. The other woman had a slight posterior subcapsular lenticular opacity and her best corrected visual acuity was 8/10 in the right eye and with her left eye she was only able to count fingers at a distance of one foot. A mutational analysis of their ARS gene revealed the presence of the homozygous missense mutation C99Y and two single nucleotide polymorphisms (-55G>C and -60G>C). The splice mutation (c.1327+4A-G) within intron 12 of the HSF4 gene, which has been previously described in Tunisian families with congenital cataract, was not found in the two probands within this family. Conclusion To the best of our knowledge, such original clinical association has not been reported previously. The association of these two autosomal recessive diseases might have occurred in this family due to a high degree of inbreeding. The C99Y mutation may be specific to the Tunisian population as it has been exclusively reported so far in only three Tunisian families with mal de Meleda. PMID:20406438

2010-01-01

16

Prevalence and perceptions about consanguineous marriages among patients presenting to family physicians, in 2001 at a Teaching Hospital in Karachi, Pakistan  

Microsoft Academic Search

Aim : Consanguineous marriages are common in Pakistan despite their declining popularity in the developed world. In the present study, a questionnaire based survey was used to record the attitudes and perceptions of consanguineous marriages among the sample population. Methods : A questionnaire was developed to collect information on the acceptability of, and percep- tions about, consanguineous marriages among patients

Waris Qidwai; Iqbal Azam Syed; Faisal M Khan

2003-01-01

17

Clinical and molecular effect on offspring of a marriage of consanguineous spinocerebellar ataxia type 7 mutation carriers: a family case report  

PubMed Central

Spinocerebellar ataxia type 7 (SCA7) is a genetic disorder characterized by degeneration of the cerebellum, brainstem, and retina that is caused by abnormal expansion of a CAG repeat located in the ATXN7 gene encoding sequence on chromosome 3p21.1. Although SCA7 is an uncommon autosomal dominant ataxia, we previously found increased prevalence of the disease in a Southeastern Mexican population. In this study, we described to our knowledge for the first time a marriage of consanguineous SCA7 mutation carriers and their offspring effect. We characterized a severely affected infantile-onset female patient whose parents and two siblings exhibited no symptoms of the disease at time of diagnosis. A comprehensive clinical analysis of the proband showed a progressive cerebellar syndrome, including gait ataxia, movement disorders, and saccadic movements, as well as hyperreflexia, visual deterioration, urinary and cardiovascular dysfunction, and impaired nerve conduction. The SCA7 mutation was detected in the proband patient. Subsequently, genetic examination using four ATXN7 gene-linked markers (three centromeric microsatellite markers [D3S1228, D3S1287, and D3S3635] and an intragenic Single Nucleotide Polymorphism [SNP-3145G/A]) revealed that the proband descends from a couple of consanguineous SCA7 mutation carriers. Genotyping analysis demonstrated that all offspring inherited only one mutant allele, and that the severe infantile-onset phenotype is caused by germinal expansion (from 37 to 72 CAG repeats) of the paternal mutant allele. Interestingly, the couple also referred a miscarriage. Finally, we found no CAA interruptions in the ATXN7 gene CAG repeats tract in this family, which might explain, at least in part, the triplet instability in the proband. PMID:25664129

Magaña, Jonathan J; Tapia-Guerrero, Yessica S; Velázquez-Pérez, Luis; Cruz-Mariño, Tania; Cerecedo-Zapata, Cesar M; Gómez, Rocío; Murillo-Melo, Nadia M; González-Piña, Rigoberto; Hernández-Hernández, Oscar; Cisneros, Bulmaro

2014-01-01

18

Consanguineous marriage among the Fulani.  

PubMed

The Fulani are a broad ethnic category of nomadic and seminomadic pastoralists and agropastoralists living in the semiarid Sahel region of sub-Saharan Africa. The Fulani are patrilineal, patrilocal, and moderately polygynous, with arranged first marriages accompanied by the payment of bridewealth, ideally in the form of cattle. Consanguineous marriage is frequent, with first or second cousin marriage preferred. In this paper we present data on levels of consanguineous marriage among the Fulani of northern Burkina Faso and test the hypothesis that inbreeding may be more frequent when there is a scarcity of cattle available, since bridewealth demands are thought to be reduced with close-kin marriage. Among 308 women's marriages, 203 (65.8%) were between kin up to and including second cousins, and 102 (33.1%) were between nonkin. Among 276 men's marriages, 196 (71.0%) were between kin up to and including second cousins, and 77 (27.9%) were between nonkin. The mean population inbreeding coefficient (alpha) was 0.0355 for women, and 0.0374 for men. No increase was found in population levels of inbreeding estimated from marriages contracted after the droughts of 1973 and 1984, which drastically reduced the Fulani's cattle stocks. However, a significantly higher rate of consanguineous marriage was found in families owning the fewest cattle. PMID:11512686

Hampshire, K R; Smith, M T

2001-08-01

19

Integration of Sequence Data from a Consanguineous Family with Genetic Data from an Outbred Population Identifies PLB1 as a Candidate Rheumatoid Arthritis Risk Gene  

PubMed Central

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P?=?0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF?=?0.042] and rs116541814 [MAF?=?0.021], combined P?=?3.2×10?6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P?=?0.049 for C-alpha test and P?=?0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. PMID:24520335

Okada, Yukinori; Diogo, Dorothee; Greenberg, Jeffrey D.; Mouassess, Faten; Achkar, Walid A. L.; Fulton, Robert S.; Denny, Joshua C.; Gupta, Namrata; Mirel, Daniel; Gabriel, Stacy; Li, Gang; Kremer, Joel M.; Pappas, Dimitrios A.; Carroll, Robert J.; Eyler, Anne E.; Trynka, Gosia; Stahl, Eli A.; Cui, Jing; Saxena, Richa; Coenen, Marieke J. H.; Guchelaar, Henk-Jan; Huizinga, Tom W. J.; Dieudé, Philippe; Mariette, Xavier; Barton, Anne; Canhão, Helena; Fonseca, João E.; de Vries, Niek; Tak, Paul P.; Moreland, Larry W.; Bridges, S. Louis; Miceli-Richard, Corinne; Choi, Hyon K.; Kamatani, Yoichiro; Galan, Pilar; Lathrop, Mark; Raj, Towfique; De Jager, Philip L.; Raychaudhuri, Soumya; Worthington, Jane; Padyukov, Leonid; Klareskog, Lars; Siminovitch, Katherine A.; Gregersen, Peter K.; Mardis, Elaine R.; Arayssi, Thurayya; Kazkaz, Layla A.; Plenge, Robert M.

2014-01-01

20

From "New Genetics" to Everyday Knowledge: Ideas about How Genetic Diseases Are Transmitted in Two Large Brazilian Families  

ERIC Educational Resources Information Center

This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected…

Santos, Silvana; Bizzo, Nelio

2005-01-01

21

A Family Study in Oman: Large, Consanguineous, Polygamous Omani Arab Pedigrees  

Microsoft Academic Search

Objective: To establish a suitable human model for the study of the genetics of complex diseases. Methods: We have selected an Omani Arab population to provide the statistical power required to study the genetics of complex diseases with confidence. This model consists of five multigenerational highly inbred pedigrees, descending from a small number of founders just a few generations ago

M. O. Hassan; S. Albarwani; S. Al Yahyaee; S. Al Haddabi; S. Rizwi; A. Jaffer; J. Al-Lawati; G. Cai; Anthony G. Comuzzie; R. A. Bayoumi

2005-01-01

22

Consanguineous marriage in Jordan.  

PubMed

We conducted a population-based study of consanguineous marriages in Jordan. About two thousand households were interviewed. First cousin marriages were encountered in 32.03%, second cousin in 6.8%, distant relation in 10.5%, and no relation in 50% of all marriages, respectively. Inbreeding coefficients were compared with those of other countries. The most important variables affecting inbreeding were social tradition, religion, education, and place of residence--urban vs. rural. Secular trends appear rather stable since the early decades of the twentieth century, especially for first cousin marriages. Jordan society showed a deeply rooted traditional behavioral pattern when inbreeding is considered. PMID:1642259

Khoury, S A; Massad, D

1992-07-15

23

Was the Darwin/Wedgwood Dynasty Adversely Affected by Consanguinity?  

NSDL National Science Digital Library

Charles Darwin, who was married to his first cousin, Emma Wedgwood, was one of the first experimentalists to demonstrate the adverse effects of inbreeding and to question the consequences of consanguineous mating. He documented the phenomenon of inbreeding depression for numerous plant species, and this caused him to worry about the health of his own children, who were often ill. To determine whether Darwin's fears were justified, we constructed a pedigree of the Darwin/Wedgwood dynasty from the large quantity of genealogical information published on these families. The inbreeding coefficients (F) computed from the pedigree show that Darwin's children were subject to a moderate level of inbreeding (F 5 0.0630), and the progeny of related families had still higher inbreeding values (e.g., F 5 0.1255 for the progeny of Henry Wedgwood, Emma Wedgwood's brother). The analysis of a sample of 25 Darwin/Wedgwood families belonging to four consecutive generations shows a statistically significant positive association between child mortality (death at or before the age of 10 years) and inbreeding coefficient detected by means of nonparametric tests (Ï? = 0.309, P = 0.040). Our findings suggest that the high childhood mortality experienced by the Darwin progeny (3 of his 10 children died at age 10 or younger) might be a result of increased homozygosity of deleterious recessive alleles produced by the consanguineous marriages within the Darwin/Wedgwood dynasty.

Tim Berra (The Ohio State University; Dept of Evolution, Ecology and Organismal Biology)

2010-05-03

24

Arranged marriage, consanguinity and epilepsy  

Microsoft Academic Search

Arranged marriage is where parents choose marital partners for their children. It is a norm in many parts of Asia and Middle East. A marriage is said to be consanguineous where the marriages are solemnized among persons with close biological relations. There is considerable overlap in arranged and consanguineous marriages with many cultures adopting both practices. Recent studies showed that

MM Mehndiratta; B Paul; P Mehndiratta Mehndiratta

25

Consanguinity and reproductive health among Arabs  

Microsoft Academic Search

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically

Ghazi O Tadmouri; Pratibha Nair; Tasneem Obeid; Mahmoud T Al Ali; Najib Al Khaja; Hanan A Hamamy

2009-01-01

26

Consanguinity, human evolution, and complex diseases  

PubMed Central

There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or closer (F ? 0.0156) and their progeny account for an estimated 10.4% of the global population. The highest rates of consanguineous marriage occur in north and sub-Saharan Africa, the Middle East, and west, central, and south Asia. In these regions even couples who regard themselves as unrelated may exhibit high levels of homozygosity, because marriage within clan, tribe, caste, or biraderi boundaries has been a long-established tradition. Mortality in first-cousin progeny is ?3.5% higher than in nonconsanguineous offspring, although demographic, social, and economic factors can significantly influence the outcome. Improving socioeconomic conditions and better access to health care will impact the effects of consanguinity, with a shift from infant and childhood mortality to extended morbidity. At the same time, a range of primarily social factors, including urbanization, improved female education, and smaller family sizes indicate that the global prevalence of consanguineous unions will decline. This shift in marriage patterns will initially result in decreased homozygosity, accompanied by a reduction in the expression of recessive single-gene disorders. Although the roles of common and rare gene variants in the etiology of complex disease remain contentious, it would be expected that declining consanguinity would also be reflected in reduced prevalence of complex diseases, especially in population isolates. PMID:19805052

Bittles, A. H.; Black, M. L.

2010-01-01

27

Consanguinity and increased risk for schizophrenia in Egypt  

PubMed Central

Background Consanguinity has been suggested as a risk factor for psychsoses in some Middle Eastern countries, but adequate control data are unavailable. Our recent studies in Egypt have shown elevated parental consanguinity rates among patients with bipolar I disorder (BP1), compared with controls. We have now extended our analyses to Schizophrenia (SZ) in the same population. Methods A case-control study was conducted at Mansoura University Hospital, Mansoura, Egypt (SZ, n = 75; controls, n = 126, and their available parents). The prevalence of consanguinity was estimated from family history data (‘self report’), followed by DNA analysis using short tandem repeat polymorphisms (STRPs, n = 63) (‘DNA-based’ rates). Results Self reported consanguinity was significantly elevated among the patients (SZ: 46.6%, controls: 19.8%, OR 3.53, 95% CI 1.88, 6.64; p = 0.000058, 1 d.f.). These differences were confirmed using DNA based estimates for coefficients of inbreeding (inbreeding coefficients as means ± standard error, cases: 0.058 ± 0.007, controls: 0.022 ± 0.003). Conclusions Consanguinity rates are signifcantly elevated among Egyptian SZ patients in the Nile delta region. The associations are similar to those observed with BP1 in our earlier study. If replicated, the substantial risk associated with consanguinity raises public health concerns. They may also pave the way for gene mapping studies. PMID:20435442

Mansour, Hader; Fathi, Warda; Klei, Lambertus; Wood, Joel; Chowdari, Kodavali; Watson, Annie; Eissa, Ahmed; Elassy, Mai; Ali, Ibtihal; Salah, Hala; Yassin, Amal; Tobar, Salwa; El-Boraie, Hala; Gaafar, Hanan; Ibrahim, Nahed E.; Kandil, Kareem; El-Bahaei, Wafaa; El-Boraie, Osama; Alatrouny, Mohamed; El-Chennawi, Farha; Devlin, Bernie; Nimgaonkar, Vishwajit L.

2010-01-01

28

Association studies in consanguineous populations  

SciTech Connect

To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients. 5 refs., 6 figs., 1 tab.

Genin, E.; Clerget-Darpous, F. [Institut National d`Etudes Demographiques, Paris (France)

1996-04-01

29

From new genetics to everyday knowledge: Ideas about how genetic diseases are transmitted in two large Brazilian families  

NASA Astrophysics Data System (ADS)

This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected with a neurodegenerative disorder, SPOAN syndrome (spastic paraplegia, optic atrophy and neuropathy), and 40 individuals of another family living with neurofibromatosis type 1 (NF1). The results indicate that families here studied have built narratives to explain the origin of genetic diseases, saying that an ancestor infected with syphilis gave rise to disorders and birthmarks transmitted to descendents.

Santos, Silvana; Bizzo, Nelio

2005-07-01

30

The frequency and effecting factors of consanguineous marriage in a group of soldiers in Ankara.  

PubMed

This cross-sectional study was carried out to investigate the frequency of consanguineous marriage in a group of army conscripts in Ankara and the factors affecting this. Of 4153 soldiers, 387 were married. The rate of marriage between first cousins was found to be 19.1%, and the overall rate of consanguineous marriage was 24.1%. Consanguineous marriage was found to be significantly prevalent among soldiers who were born in and still living in the Eastern region; among those who lived in villages; among those whose parents as well as themselves had low educational levels; and among those whose marriages were arranged by their families. Neither the payment of bride-price nor the presence of consanguinity between parents was a significant factor for consanguineous marriage. In addition, the age of the soldier and the age at marriage were significantly lower among soldiers married to first cousins than among soldiers whose marriages were not consanguineous. PMID:16082860

Kir, Tayfun; Güleç, Mahir; Bakir, Bilal; Ho?jgönül, Esat; Tümerdem, Nazmi

2005-07-01

31

Is There a Significant Trend in Prevalence of Consanguineous Marriage in Tehran? A Review of Three Generations  

Microsoft Academic Search

Consanguineous marriage is a common practice in Iran. The present study surveyed the trend in consanguineous marriage across\\u000a three generations of Iranians. Index cases, consisting of 400 individuals attending the diabetes and osteoporosis clinic in\\u000a Shariati Hospital, were interviewed. Data on consanguinity status for 1789 marriages within the index cases’ families were\\u000a obtained. Generation 1 consisted of marriages contracted before

Seyed Mohammad Akrami; Vahideh Montazeri; Somaieh Rashid Shomali; Ramin Heshmat; Bagher Larijani

2009-01-01

32

Consanguinity in South America: Demographic Aspects  

Microsoft Academic Search

A sample of 53,552 nonmalformed liveborn infants was ascertained by the Latin-American Collaborative Study of Congenital Malformations between 1967 and 1996. The mean consanguinity rate was 0.96%, with significantly higher values in Brazil and Venezuela, and lower in Argentina. Low paternal education and occupation levels were positively associated with consanguinity. First-cousin matings represented almost half of all consanguineous couples. The

Rosa Liascovich; Mónica Rittler; Eduardo E. Castilla

2001-01-01

33

Consanguinity and Neonatal Death: A Nested Case-Control Study  

PubMed Central

Objective: Although numerous studies have found higher rates of abortion and still births following consanguinity (familial marriages), the question of whether consanguinity significantly increases the risk of neonatal death has inadequately been addressed.This study aims to evaluate familial marriage effects on neonatal death in rural areas in Iran. Materials and methods: In this nested case-control study, 6900 newbornswho were born in rural areas of Kohgiluyeh and Boyerahmad Province (South-West of Iran)were followed till the end of neonatal period, and neonatal death was the outcome of interest. Subsequently 97 cases and 97 controls were selected in study cohort by using risk set sampling model. Crude and adjusted odds ratios (OR) were estimated by usinga conditional logistic regression model. Results: In the final model, prematurity (OR = 5.57), low birthweight (LBW) (OR = 7.68), consanguinity (first cousins) (OR = 5.23), C-section (OR = 7.27), birth rank more than 3 (OR = 6.95) and birthsinterval less than 24 months (OR = 4.65) showed significant statistical association with neonatal mortality (p < 0.05). Conclusion: According to our findings, after adjusting the effects of other significant risk factors, familial marriageto first cousins is considered asan important risk factor for neonatal death.

Chaman, Reza; Gholami Taramsari, Mahshid; Khosravi, Ahmad; Amiri, Mohammad; Holakouie Naieni, Kourosh; Yunesian, Masoud

2014-01-01

34

Large families of mutually singular Radon measures  

E-print Network

Large families of mutually singular Radon measures David H. Fremlin & Grzegorz Plebanek \\Lambda mutually singular Radon probability measures. 1. Introduction. We present here a partial answer with a family (¯ s ) s2S of mu­ tually singular Radon measures on X such that #(S) ? #(X)? In section 2 we

Plebanek, Grzegorz

35

Asteroid families classification: Exploiting very large datasets  

NASA Astrophysics Data System (ADS)

The number of asteroids with accurately determined orbits increases fast, and this increase is also accelerating. The catalogs of asteroid physical observations have also increased, although the number of objects is still smaller than in the orbital catalogs. Thus it becomes more and more challenging to perform, maintain and update a classification of asteroids into families. To cope with these challenges we developed a new approach to the asteroid family classification by combining the Hierarchical Clustering Method (HCM) with a method to add new members to existing families. This procedure makes use of the much larger amount of information contained in the proper elements catalogs, with respect to classifications using also physical observations for a smaller number of asteroids. Our work is based on a large catalog of high accuracy synthetic proper elements (available from AstDyS), containing data for >330,000 numbered asteroids. By selecting from the catalog a much smaller number of large asteroids, we first identify a number of core families; to these we attribute the next layer of smaller objects. Then, we remove all the family members from the catalog, and reapply the HCM to the rest. This gives both satellite families which extend the core families and new independent families, consisting mainly of small asteroids. These two cases are discriminated by another step of attribution of new members and by merging intersecting families. This leads to a classification with 128 families and currently 87,095 members. The number of members can be increased automatically with each update of the proper elements catalog; changes in the list of families are not automated. By using information from absolute magnitudes, we take advantage of the larger size range in some families to analyze their shape in the proper semimajor axis vs. inverse diameter plane. This leads to a new method to estimate the family age, or ages in cases where we identify internal structures. The analysis of the plot above evidences some open problems but also the possibility of obtaining further information of the geometrical properties of the impact process. The results from the previous steps are then analyzed, using also auxiliary information on physical properties including WISE albedos and SDSS color indexes. This allows to solve some difficult cases of families overlapping in the proper elements space but generated by different collisional events. The families formed by one or more cratering events are found to be more numerous than previously believed because the fragments are smaller. We analyze some examples of cratering families (Massalia, Vesta, Eunomia) which show internal structures, interpreted as multiple collisions. We also discuss why Ceres has no family.

Milani, Andrea; Cellino, Alberto; Kneževi?, Zoran; Novakovi?, Bojan; Spoto, Federica; Paolicchi, Paolo

2014-09-01

36

First steps in exploring prospective exome sequencing of consanguineous couples.  

PubMed

Consanguinity is one of the most frequent risk factors for congenital disorders. In theory, prospective exome sequencing of consanguineous couples could identify couples who both are carriers of autosomal recessive diseases, and empower such couples to make informed reproductive decisions. To investigate this, we sent blood samples to our laboratory of four pairs of consanguineous parents having one or more children affected by an autosomal recessive disorder, without revealing any diagnostic information. The study was restricted to find identical, previously described, or evidently pathogenic mutations in both parents of each couple, in over 400 genes known to result in severe autosomal recessive disorders. Out of the six autosomal recessive disorders known to the four couples studied, two were correctly identified. Carrier status of one not previously known autosomal recessive disorder was discovered. As expected, given the pipeline used, large deletions, mutations in genes not present in the gene list, mutations outside the exons and consensus splice sites, and mutations that were not evidently pathogenic and previously not reported, were not identified. The restriction to detecting only couples with identical mutations diminishes the risk of revealing unsolicited findings and shortens the time needed for analysis, but also results in missing couples with different mutations in the same gene. In addition to the proposed pipeline, couples should be offered testing for carrier status of frequent disorders that can present themselves by large deletions, non-exonic mutations or compound heterozygous mutations (e.g. thalassemia, spinal muscular atrophy, cystic fibrosis). Even though sensitivity is reduced, offering exome sequencing prospectively will increase reproductive options for consanguineous couples. PMID:25281896

Teeuw, Marieke; Waisfisz, Quinten; Zwijnenburg, Petra J G; Sistermans, Erik A; Weiss, Marjan M; Henneman, Lidewij; ten Kate, Leo P; Cornel, Martina C; Meijers-Heijboer, Hanne

2014-01-01

37

Phenotypic differences in a large family with Kennedy's disease from the Middle Black Sea region of Turkey.  

PubMed

We report the clinical and electrophysiological features of a large Turkish family with genetically confirmed X-linked spinal and bulbar muscular atrophy (SBMA). Family members were identified by field work. A detailed history was obtained from each subject, and each subject received a detailed neurological examination. To confirm the CAG repeat expansion in the AR gene, genomic DNA was extracted from the peripheral blood of patients. The family consisted of 128 individuals over five generations, with two consanguineous parents, one slightly affected female, and 12 affected males with SBMA. We studied the five surviving male patients and one surviving female carrier. The age at disease onset, phenotypic features, and disease severity varied among the family members. DNA analysis was performed on five individuals, belonging to five generations of the family. Four affected males and a slightly affected female carrier were shown to carry an expanded CAG repeat in the androgen receptor gene. This family report is consistent with previous studies suggesting that SBMA may be present with a wide clinical spectrum in affected family members. Further descriptions of SBMA affected families with different ethnic backgrounds may assist in identifying possible phenotypic and genetic features of the disease. PMID:20184516

Karaer, Hatice; Kaplan, Yüksel; Kurt, Semiha; Gundogdu, Asli; Erdo?an, Begüm; Ba?ak, Nazli A

2010-01-01

38

A novel CLDN16 mutation in a large family with familial hypomagnesaemia with hypercalciuria and nephrocalcinosis  

PubMed Central

Background Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is a rare tubulopathy leading to renal calcification and progressive renal failure. Case presentation We report a consanguineous Arab family (of Qatari origin) with 7 affected siblings with variable phenotypes including hypomagnesaemia, hypercalciuria, nephrocalcinosis and renal stones. Presenting features included haematuria and recurrent urinary tract infections. As the biochemical and clinical phenotypes of this family resembled familial hypomagnesaemia with hypercalciuria and nephrocalcinosis, we performed genetic investigation in order to provide a precise molecular diagnosis. We screened all coding regions of the CLDN16 gene and identified a novel mutation (c.G647A, p.R216H) which was found homozygously in the six severely affected cases, who manifested significant nephrocalcinosis, often nephrolithiasis and sometimes reduced GFR. Parents were both heterozygous for the mutation and, together with children carrying the mutation in its heterozygous state, exhibited mild or no biochemical phenotypes. Conclusion Mutations in CLDN16 underlie familial hypomagnesaemia with hypercalciuria and nephrocalcinosis but remain a rare cause of nephrocalcinosis and nephrolithiasis. Management includes reduction of hypercalciuria with thiazide diuretics, correction of serum magnesium and close monitoring of renal function given the significant risk of end stage renal failure with this inherited form of nephrocalcinosis. PMID:24321194

2013-01-01

39

A Novel COL4A3 Mutation Causes Autosomal-Recessive Alport Syndrome in a Large Turkish Family  

PubMed Central

Background: Alport syndrome (AS) is a genetically heterogeneous disorder that is characterized by hematuria, progressive renal failure typically resulting in end-stage renal disease, sensorineural hearing loss, and variable ocular abnormalities. Only 15% of cases with AS are autosomal recessive and are caused by mutations in the COL4A3 or COL4A4 genes, encoding type IV collagen. Methods: Clinical data in a large consanguineous family with four affected members were reviewed, and genomic DNA was extracted. For mapping, 15 microsatellite markers flanking COL4A3, COL4A4, and COL4A5 in 16 family members were typed. For mutation screening, all coding exons of COL4A3 were polymerase chain reaction- amplified and Sanger-sequenced from genomic DNA. Results: The disease locus was mapped to chromosome 2q36.3, where COL4A3 and COL4A4 reside. Sanger sequencing revealed a novel mis-sense mutation (c.2T>C; p.M1T) in exon 1 of COL4A3. The identified nucleotide change was not found in 100 healthy ethnicity-matched controls via Sanger sequencing. Conclusions: We present a large consanguineous Turkish family with AS that was found to have a COL4A3 mutation as the cause of the disease. Although the relationship between the various genotypes and phenotypes in AS has not been fully elucidated, detailed clinical and molecular analyses are helpful for providing data to be used in genetic counseling. It is important to identify new mutations to clarify their clinical importance, to assess the prognosis of the disease, and to avoid renal biopsy for final diagnosis. PMID:23297803

Uzak, Asli Subasioglu; Tokgoz, Bulent; Dundar, Munis

2013-01-01

40

Consanguinity pattern and heritability of Vitiligo in Arar, Saudi Arabia  

PubMed Central

Context: Epidemiological studies have shown that vitiligo is a complex trait, involving combinations of pathogenic effects of multiple susceptibility genes as well as environmental risk factors. Aim: To observe whether consanguinity increased the incidence of vitiligo in Saudi patients from Arar. Patients and Methods: This study included 69 Saudi patients with vitiligo and their families. These patients, selected from the experience specialist dermatology center in Arar, from April 2011 to 2012, were interviewed by a dermatologist to confirm the diagnosis and complete a questionnaire. Results: A total of 69 patients, 40 males and 29 females were selected. Their mean age was 34.5 ± 11.8 years with the median age of 23 years. The mean age at onset of disease was 27.9 ± 12.9 years. The mean duration of the disease was 9.7 ± 5.3 years. The frequency of focal, vulgaris, universal, and acrofacial subtypes was 22 (31.9%), 21 (30.4%), 8 (11.6%), and 18 (26.1%), respectively. A positive family history of vitiligo was obtained in 45 (65.2%) cases. A comparison of the frequency of vitiligo among siblings in relation to the general population was more in accord with the multifactorial model. Conclusion: Consanguinity in marriage increases the incidence of the disease. Therefore, genetic counseling and premarital examination would be important contributions to lower the prevalence of vitiligo. PMID:24696629

Alenizi, Dhaifallah A.

2014-01-01

41

Consanguine Calculations Input File: blood.in  

E-print Network

1 of 20 Problem A+ Consanguine Calculations Input File: blood.in Every person's blood has 2 markers in a particular ABO blood type for that person. Combination ABO Blood Type AA A AB AB AO A BB B BO B OO O Likewise, every person has two alleles for the blood Rh factor, represented by the characters + and -. Someone who

California at Berkeley, University of

42

Consanguinity and its sociodemographic differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan.  

PubMed

Kashmiri population in the northeast of Pakistan has strong historical, cultural and linguistic affinities with the neighbouring populations of upper Punjab and Potohar region of Pakistan. However, the study of consanguineous unions, which are customarily practised in many populations of Pakistan, revealed marked differences between the Kashmiris and other populations of northern Pakistan with respect to the distribution of marriage types and inbreeding coefficient (F). The current descriptive epidemiological study carried out in Bhimber district of Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin unions were the predominant type of marriages and constituted 50.13% of total marital unions. The estimates of inbreeding coefficient were higher in the literate subjects, and consanguinity was witnessed to be rising with increasing literacy level. Additionally, consanguinity was observed to be associated with ethnicity, family structure, language, and marriage arrangements. Based upon these data, a distinct sociobiological structure, with increased stratification and higher genomic homozygosity, is expected for this Kashmiri population. In this communication, we present detailed distribution of the types of marital unions and the incidences of consanguinity and inbreeding coefficient (F) across various sociodemographic strata of Bhimber/Mirpuri population. The results of this study would have implication not only for other endogamous populations of Pakistan but also for the sizeable Kashmiri community immigrated to Europe. PMID:25076667

Jabeen, Nazish; Malik, Sajid

2014-06-01

43

Consanguinity and Its Sociodemographic Differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan  

PubMed Central

ABSTRACT Kashmiri population in the northeast of Pakistan has strong historical, cultural and linguistic affinities with the neighbouring populations of upper Punjab and Potohar region of Pakistan. However, the study of consanguineous unions, which are customarily practised in many populations of Pakistan, revealed marked differences between the Kashmiris and other populations of northern Pakistan with respect to the distribution of marriage types and inbreeding coefficient (F). The current descriptive epidemiological study carried out in Bhimber district of Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin unions were the predominant type of marriages and constituted 50.13% of total marital unions. The estimates of inbreeding coefficient were higher in the literate subjects, and consanguinity was witnessed to be rising with increasing literacy level. Additionally, consanguinity was observed to be associated with ethnicity, family structure, language, and marriage arrangements. Based upon these data, a distinct sociobiological structure, with increased stratification and higher genomic homozygosity, is expected for this Kashmiri population. In this communication, we present detailed distribution of the types of marital unions and the incidences of consanguinity and inbreeding coefficient (F) across various sociodemographic strata of Bhimber/Mirpuri population. The results of this study would have implication not only for other endogamous populations of Pakistan but also for the sizeable Kashmiri community immigrated to Europe. PMID:25076667

Jabeen, Nazish

2014-01-01

44

Endogamy, consanguinity and community genetics  

Microsoft Academic Search

The population of India is composed of many thousands of subpopulations, divided by geography, language, religion and caste or biraderi (patrilineage) boundaries, with endogamous marriage the norm. The net effect has been the creation of multiple genetic isolates with indi- vidual mutation profiles, but to date the clinical con- sequences of this highly complex differentiation have been largely ignored. In

A. H. BITTLES

2003-01-01

45

Endogamy, consanguinity and community genetics  

Microsoft Academic Search

The population of India is composed of many thousands of subpopulations, divided by geography, language, religion and caste\\u000a or biraderi (patrilineage) boundaries, with endogamous marriage the norm. The net effect has been the creation of multiple\\u000a genetic isolates with individual mutation profiles, but to date the clinical consequences of this highly complex differentiation\\u000a have been largely ignored. In contrast, the

Alan Bittles

2002-01-01

46

Genome-Wide Homozygosity Analysis Reveals HADH Mutations as a Common Cause of Diazoxide-Responsive Hyperinsulinemic-Hypoglycemia in Consanguineous Pedigrees  

PubMed Central

Context and Objective: Recessive mutations in the hydroxyacyl-CoA dehydrogenase (HADH) gene encoding the enzyme 3-hydroxyacyl-CoA dehydrogenase are a rare cause of diazoxide-responsive hyperinsulinemic hypoglycemia (HH) with just five probands reported to date. HADH deficiency in the first three identified patients was associated with detectable urinary 3-hydroxyglutarate and raised plasma 3-hydroxybutyryl-carnitine levels, but two recent cases did not have abnormal urine organic acids or acylcarnitines. Research Design and Methods: We studied 115 patients with diazoxide-responsive HH in whom the common genetic causes of HH had been excluded. No patients were reported to have abnormal acylcarnitines or urinary organic acids. Homozygosity mapping was undertaken in probands from 13 consanguineous pedigrees to search for regions harboring mutations that are identical by descent. Results: HADH sequencing was performed after genome-wide single nucleotide polymorphism analysis revealed a large shared region of homozygosity spanning the HADH locus in six unrelated probands. Homozygous mutations were identified in three of these patients and in a further two probands from consanguineous families. HADH analysis in the remainder of the cohort identified mutations in a further six probands for whom consanguinity was not reported, but who originated from countries with high rates of consanguinity. Six different HADH mutations were identified in 11/115 (10%) patients tested. Conclusion: HADH mutations are a relatively common cause of diazoxide-responsive HH with a frequency similar to that of GLUD1 and HNF4A mutations. We recommend that HADH sequence analysis is considered in all patients with diazoxide-responsive HH when recessive inheritance is suspected. PMID:21252247

Flanagan, Sarah E.; Patch, Ann-Marie; Locke, Jonathan M.; Akcay, Teoman; Simsek, Enver; Alaei, Mohammadreza; Yekta, Zeinab; Desai, Meena; Kapoor, Ritika R.; Hussain, Khalid

2011-01-01

47

The changing profile of consanguinity rates in Bahrain, 1990-2009.  

PubMed

Consanguineous marriage is traditional and respected in most communities of North Africa, the Middle East and West Asia, including Bahrain, with intra-familial unions accounting for 20-50+% of all marriages. Significant secular changes in consanguinity rates have been reported in recent decades in different populations. Among parents of 14,237 newborns in Bahrain in 2008-2009, the total consanguinity and first cousin marriage rates over a period of four months in 2008 were 10.9% and 6.9% respectively, while during all of 2009 the rates were 11.4% and 6.8% respectively. The study confirms that over a ten-year period first cousin marriage rates in Bahrain have declined from 24% to nearly 7%. Although advice against cousin marriages was not attempted at any stage in the comprehensive community genetics programmes in Bahrain, increasing the literacy of the public and of the health care providers on prevention strategies for genetic diseases could have contributed to this decline in consanguinity rate in Bahrain. PMID:22123433

Al-Arrayed, Shaikha; Hamamy, Hanan

2012-05-01

48

Managing Large Qualitative Data Sets in Family Research  

Microsoft Academic Search

The authors describe two complementary data management techniques-family case summaries and computer generated matrices-and their contribution to the analytic goals of a study offamily response to childhood chronic illness. Family case summaries enabled the investigators to reduce a large qualitative data set in a way that preserved thefamilyfocus of the research. The use of a database management software system contributed

Kathleen A. Knafl; Lioness Ayres

1996-01-01

49

Contribution of social and cultural factors to the decline in consanguinity in south India.  

PubMed

The data from the National Family Health Survey, 1992-1993, show that the extent of consanguinity is high (34.7 percent) in South India; 26.2 percent of women married close blood relatives, and 8.5 percent of women married distant blood relatives. A definite downward trend in the proportion of marriages between close blood relatives is observed. Education, age at marriage, religion and caste, and urban-rural childhood residence have significant independent effects on consanguinity. The multinomial logistic regression analysis reveals that in South India the downward trend in the proportion of marriages between close blood relatives is entirely explained by rising age at marriage and women's education over time. PMID:12055694

Audinarayana, N; Krishnamoorthy, S

2000-01-01

50

A Homozygous CARD9 Mutation in a Family with Susceptibility to Fungal Infections  

Microsoft Academic Search

Background Chronic mucocutaneous candidiasis may be manifested as a primary immunodefi- ciency characterized by persistent or recurrent infections of the mucosa or the skin with candida species. Most cases are sporadic, but both autosomal dominant in- heritance and autosomal recessive inheritance have been described. Methods We performed genetic studies in 36 members of a large, consanguineous five-gener- ation family, in

Erik-Oliver Glocker; Andre Hennigs; Mohammad Nabavi; Alejandro A. Schäffer; Cristina Woellner; Ulrich Salzer; Dietmar Pfeifer; Hendrik Veelken; Klaus Warnatz; Fariba Tahami; Sarah Jamal; Annabelle Manguiat; Nima Rezaei; Ali Akbar Amirzargar; Alessandro Plebani; Nicole Hannesschläger; Olaf Gross; Jürgen Ruland; Bodo Grimbacher

2010-01-01

51

Incidence of Friedreich ataxia in Italy estimated from consanguineous marriages.  

PubMed Central

The frequency of consanguineous marriages up to second-cousin degree has been carefully established in the past for each of the 95 Italian provinces using the Archive of about 500,000 dispensations given by the Catholic church for such marriages over a 55-year period. It has therefore been possible to compare the frequency of consanguineous marriages observed among 83 couples of parents of Friedreich patients with the frequency of consanguineous marriages of the same degree in the different Italian provinces during the same years. From these data, an estimate of the incidence of the disease has been obtained for the whole nation (between 1/22,000 and 1/25,000). In Southern Italy, where 16 out of the 18 consanguineous marriages among Friedreich parents are concentrated, the incidence of the disease is similar (between 1/25,000 and 1/28,000). This study indicates that the Archive of consanguinity existing in Italy allows a reliable comparison of the frequency of consanguineous marriages among parents of patients with that of the general population. The same method can therefore be applied to the study of incidence of other autosomal recessive disorders in Italy. PMID:6859045

Romeo, G; Menozzi, P; Ferlini, A; Fadda, S; Di Donato, S; Uziel, G; Lucci, B; Capodaglio, L; Filla, A; Campanella, G

1983-01-01

52

[Factors influencing the frequency of consanguineous marriages in Japan].  

PubMed

A survey of consanguineous marriages in Japan was conducted through questionnaires in 1983. The total number of couples studied was 9225, chosen from 6 widely different areas of Japan. The rates of first cousin marriages and of total consanguineous marriages for all areas were 1.6% and 3.9%, respectively. The rate of total consanguineous marriages was 10 times higher in Fukue-Shi (7.9%) than Asahikawa city area (.78%). The rate of total consanguineous marriages decreased with the marriage year in Japan, where the rate of first cousin marriages has changed remarkably. The rates of consanguineous marriages were estimated according to marital distance between birth places, socioeconomic classes, religion, marriage form, opportunity of encounter, and motivation towards marriage. Among educational groups, the rate was highest in graduates of junior high school for husbands and wives, and the rate was lowest in college or university graduates. Occupationally, the rate was the highest in agriculture, forestry, and fishery for husbands and wives, and the rate was lowest among salesmen for husbands and in professional occupations and researchers for wives. As for opportunities of encounter, the rate was 22-29 times higher in the group for friendship from the time of childhood (25.8%) than in those for school, workplace, and social gatherings (1.2%) and for chance meetings (.9%). A recommendation by parents and relatives was the most frequent reason for consanguineous marriage for both husbands and wives, followed by knowledge of the partner by relatives. PMID:12314927

Imaizumi, Y

1987-04-01

53

Oculocerebral syndrome with hypopigmentation (Cross syndrome). Report of two siblings born to consanguineous parents.  

PubMed

In this report we describe two siblings, a 17-year-old male and his deceased sister, born to consanguineous parents, and presenting an oculocerebral syndrome with hypopigmentation as first delineated by Cross in 1967. In addition to the cutaneous hypopigmentation, both presented deep mental retardation and spastic tetraplegia with athetoid movements. A remarkable finding in this family is that a third sibling, an otherwise normal 23-year-old male, presents the same hypopigmentation with white-grey hair colour as his two severely affected siblings. PMID:3191612

Fryns, J P; Dereymaeker, A M; Heremans, G; Marien, J; van Hauwaert, J; Turner, G; Hockey, A; van den Berghe, H

1988-08-01

54

Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred  

PubMed Central

The biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1–13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans. PMID:21885617

Gulsuner, Suleyman; Tekinay, Ayse Begum; Doerschner, Katja; Boyaci, Huseyin; Bilguvar, Kaya; Unal, Hilal; Ors, Aslihan; Onat, O. Emre; Atalar, Ergin; Basak, A. Nazli; Topaloglu, Haluk; Kansu, Tulay; Tan, Meliha; Tan, Uner; Gunel, Murat; Ozcelik, Tayfun

2011-01-01

55

Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred.  

PubMed

The biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1-13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans. PMID:21885617

Gulsuner, Suleyman; Tekinay, Ayse Begum; Doerschner, Katja; Boyaci, Huseyin; Bilguvar, Kaya; Unal, Hilal; Ors, Aslihan; Onat, O Emre; Atalar, Ergin; Basak, A Nazli; Topaloglu, Haluk; Kansu, Tulay; Tan, Meliha; Tan, Uner; Gunel, Murat; Ozcelik, Tayfun

2011-12-01

56

Consanguinity and other marriage market effects of a wealth shock in Bangladesh.  

PubMed

This paper uses a wealth shock from the construction of a flood protection embankment in rural Bangladesh coupled with data on the universe of all 52,000 marriage decisions between 1982 and 1996 to examine changes in marital prospects for households protected by the embankment relative to unprotected households living on the other side of the river. We use difference-in-difference specifications to document that brides from protected households commanded larger dowries, married wealthier households, and became less likely to marry biological relatives. Financial liquidity-constrained households appear to use within-family marriage (in which one can promise ex-post payments) as a form of credit to meet up-front dowry demands, but the resultant wealth shock for households protected by the embankment relaxed this need to marry consanguineously. Our results shed light on the socioeconomic roots of consanguinity, which carries health risks for offspring but can also carry substantial benefits for the families involved. PMID:23619998

Mobarak, Ahmed Mushfiq; Kuhn, Randall; Peters, Christina

2013-10-01

57

Oculocutaneous albinism and consanguineous marriage among Spanish Gitanos or Calé--a study of 83 cases.  

PubMed

This paper studies 83 cases of oculocutaneous albinism (OCA) in family networks of Gitanos in southeastern Spain, and analyzes their sustained inbreeding patterns and complex genealogical relationships. It is based in the family and genealogy reconstitution of the Gitano population of 22 contiguous localities using ethnographic and historical demography methods. The study found a prevalence of OCA among Gitanos in the area of about 1: 1,200. Most of the cases belong to three extended kin networks in which consanguineous marriages have been common for generations. In these networks there are other cases of visual and auditive congenital anomalies, and other birth defects such as brachydactily, polydactily, neurological defects, Potter Sequence, etc. In 61 OCA cases it was possible to trace inbreeding links with a depth of three to nine generations. For these cases the estimated alpha (average of the inbreeding coefficient, F) is 0.0222. Relationships between the parents of people affected are of three types: close, as between first or second cousins; distant, as between third or fourth cousins, and non-existent, as in mixed marriages. In most cases, however, persons with albinism are linked by multiple consanguineous links. Albinism seems to be a visible example of a high prevalence of birth defects in this minority, associated with founder effects, sustained inbreeding and high fertility rates. These conditions derive from Gitano's marriage preferences and pronatalist strategies. In turn, these strategies have to be related to the exclusion, persecution and segregation that Spanish Gypsies have suffered for centuries. PMID:24308209

Gamella, Juan F; Carrasco-Muñoz, Elisa Martín; Núñez Negrillo, Ana María

2013-09-01

58

Consanguineous Marriages in the Sikh Community of Swat, NWFP, Pakistan  

Microsoft Academic Search

Marriages among the Sikh minority of the Districts of Swat, Bunair and Shangla (NWFP, Pakistan) were studied where the frequency of consanguineous marriages was found to be 21%. Marriages with distant relatives were 29.4% in the population. The inbreeding coefficient for the population was calculated to be 0.0127. Only three types of first cousin marriages (MSD, MBD and FSD) were

Abdul Wahab; Mahmud Ahmad

2005-01-01

59

Letters to the Editor CONSANGUINITY AND HETEROGENEITY: CYSTIC FIBROSIS  

E-print Network

Letters to the Editor CONSANGUINITY AND HETEROGENEITY: CYSTIC FIBROSIS NEED NOT BE HOMOGENEOUS, ET AL.: Incidence in Italy, genetic heterogeneity, and segregation analysis of cystic fibrosis. Am J Hum Genet 37:338-349, 1985 2. Tsui LC, BUCHWALD M, BARKER D, ET AL.: Cystic fibrosis locus defined

Botstein, David

60

Airfoil family design for large offshore wind turbine blades  

NASA Astrophysics Data System (ADS)

Wind turbine blades size has scaled-up during last years due to wind turbine platform increase especially for offshore applications. The EOLIA project 2007-2010 (Spanish Goverment funded project) was focused on the design of large offshore wind turbines for deep waters. The project was managed by ACCIONA Energia and the wind turbine technology was designed by ACCIONA Windpower. The project included the design of a wind turbine airfoil family especially conceived for large offshore wind turbine blades, in the order of 5MW machine. Large offshore wind turbines suffer high extreme loads due to their size, in addition the lack of noise restrictions allow higher tip speeds. Consequently, the airfoils presented in this work are designed for high Reynolds numbers with the main goal of reducing blade loads and mantainig power production. The new airfoil family was designed in collaboration with CENER (Spanish National Renewable Energy Centre). The airfoil family was designed using a evolutionary algorithm based optimization tool with different objectives, both aerodynamic and structural, coupled with an airfoil geometry generation tool. Force coefficients of the designed airfoil were obtained using the panel code XFOIL in which the boundary layer/inviscid flow coupling is ineracted via surface transpiration model. The desing methodology includes a novel technique to define the objective functions based on normalizing the functions using weight parameters created from data of airfoils used as reference. Four airfoils have been designed, here three of them will be presented, with relative thickness of 18%, 21%, 25%, which have been verified with the in-house CFD code, Wind Multi Block WMB, and later validated with wind tunnel experiments. Some of the objectives for the designed airfoils concern the aerodynamic behavior (high efficiency and lift, high tangential coefficient, insensitivity to rough conditions, etc.), others concern the geometry (good for structural design, compatibility for the different airfoil family members, etc.) and with the ultimate objective that the airfoils will reduce the blade loads. In this paper the whole airfoil design process and the main characteristics of the airfoil family are described. Some force coefficients for the design Reynolds number are also presented. The new designed airfoils have been studied with computational calculations (panel method code and CFD) and also in a wind tunnel experimental campaign. Some of these results will be also presented in this paper.

Méndez, B.; Munduate, X.; San Miguel, U.

2014-06-01

61

Complex genetic background in a large family with Brugada syndrome.  

PubMed

The Brugada syndrome (BrS) is an inherited arrhythmia characterized by ST-segment elevation in V1-V3 leads and negative T wave on standard ECG. BrS patients are at risk of sudden cardiac death (SCD) due to ventricular tachyarrhythmia. At least 17 genes have been proposed to be linked to BrS, although recent findings suggested a polygenic background. Mutations in SCN5A, the gene coding for the cardiac sodium channel Nav1.5, have been found in 15-30% of index cases. Here, we present the results of clinical, genetic, and expression studies of a large Iranian family with BrS carrying a novel genetic variant (p.P1506S) in SCN5A. By performing whole-cell patch-clamp experiments using HEK293 cells expressing wild-type (WT) or p.P1506S Nav1.5 channels, hyperpolarizing shift of the availability curve, depolarizing shift of the activation curve, and hastening of the fast inactivation process were observed. These mutant-induced alterations lead to a loss of function of Nav1.5 and thus suggest that the p.P1506S variant is pathogenic. In addition, cascade familial screening found a family member with BrS who did not carry the p.P1506S mutation. Additional next generation sequencing analyses revealed the p.R25W mutation in KCNH2 gene in SCN5A-negative BrS patients. These findings illustrate the complex genetic background of BrS found in this family and the possible pathogenic role of a new SCN5A genetic variant. PMID:25626866

Saber, Siamak; Amarouch, Mohamed-Yassine; Fazelifar, Amir-Farjam; Haghjoo, Majid; Emkanjoo, Zahra; Alizadeh, Abolfath; Houshmand, Massoud; Gavrilenko, Alexander V; Abriel, Hugues; Zaklyazminskaya, Elena V

2015-01-01

62

Consanguinity and late fertility: spatial analysis reveals positive association patterns.  

PubMed

The role of consanguinity on human complex traits is an important and controversial issue. In this work we focused on the Sardinian population and examined the effect of consanguineous unions on late female fertility. During the last century the island has been characterized by a high incidence of marriages between relatives, favoured by socio economic conditions and geographical isolation, and by high fertility despite a widespread tendency to delay reproduction. Through spatial analysis techniques, we explored the geographical heterogeneity of consanguinity and late fertility, and identified in Central-Eastern Sardinia a common area with an excess of both traits, where the traits are positively associated. We found that their association did not significantly affect women's fertility in the area, despite the expected negative role of both traits. Intriguingly, this critical zone corresponds well to areas reported by previous studies as being peculiar for a high frequency of centenarians and for lower risk in pregnancy outcome. The proposed approach can be generally exploited to identify target populations on which socioeconomic, biodemographic and genetic data can be collected at the individual level, and deeper analyses carried out to disentangle the determinants of complex biological traits and to investigate their association. PMID:25441534

Lisa, Antonella; Astolfi, Paola; Zei, Gianna; Tentoni, Stefania

2015-01-01

63

Large families of quaternary sequences with low correlation  

Microsoft Academic Search

A family of quaternary (Z4-alphabet) sequences of length L=2r-1, size M⩾L2+3L+2, and maximum nontrivial correlation parameter Cmax⩽2?(L+1)+1 is presented. The sequence family always contains the four-phase family 𝒜. When r is odd, it includes the family of binary Gold sequences. The sequence family is easily generated using two shift registers, one binary, the other quaternary. The distribution of correlation values

P. Vijay Kumar; Tor Helleseth; A. Robert Calderbank; A. Roger Hammons Jr.

1996-01-01

64

Hurler disease (mucopolysaccharidosis type IH): clinical features and consanguinity in Tunisian population  

PubMed Central

Mucopolysaccharidosis type I (MPS I) was a group of rare autosomal recessive disorder caused by the deficiency of the lysosomal enzyme, alpha -L -iduronidase, and the resulting accumulation of undergraded dematan sulfate and heparan sulfate. MPS I patients have a wide range of clinical presentations, that makes it difficult to predict patient phenotype which is needed for genetic counseling and also impedes the selection and evaluation of patients undergoing therapy bone marrow transplantation. Aim of the study consanguinity rates have been determined among 14 families with mucopolysaccharidosis type I, seen in the pediatric departments of different geographic areas of Tunisia (Central and Southern areas) for the period August 2004 - August 2011 in order to investigate the relation between consanguinity and this disorder. Patients and methods Clinical and molecular analyses confirmed the diagnosis for MPS type I in the studied families. Results Most of the Tunisian MPS I patients have been identified at the homozygous status: p.P533R mutation (7 homozygous and one double heterozygous p.L578Q/p.P533R patients; 41.66% of all the investigated MPSI patients), p.F177S (1 homozygous patient; 5.55%), p.L530fs (1 patient; 5.55%), p.Y581X (2 patients; 11.11%), p.F602X (3 patients; 16.66%), p.R628X (1 patient; 5.55%). Another mutation: p.L578Q has been identified at the heterozygous status in the only double heterozygous p.L578Q/p.P533R case. Part of the mutations was the result of a founder effect. These described points are the consequences of the high rate of consanguinity. Conclusion The high frequency of p.P533R mutation could be explained by the high degree of inbreeding. This is due to the richness of the genetic background of the studied population. A multidisciplinary approach is essential to develop adequate preventive program adapted to the social, cultural, and economic context. PMID:22074387

2011-01-01

65

Predicting function from sequence in a large multifunctional toxin family.  

PubMed

Venoms contain active substances with highly specific physiological effects and are increasingly being used as sources of novel diagnostic, research and treatment tools for human disease. Experimental characterisation of individual toxin activities is a severe rate-limiting step in the discovery process, and in-silico tools which allow function to be predicted from sequence information are essential. Toxins are typically members of large multifunctional families of structurally similar proteins that can have different biological activities, and minor sequence divergence can have significant consequences. Thus, existing predictive tools tend to have low accuracy. We investigated a classification model based on physico-chemical attributes that can easily be calculated from amino-acid sequences, using over 250 (mostly novel) viperid phospholipase A? toxins. We also clustered proteins by sequence profiles, and carried out in-vitro tests for four major activities on a selection of isolated novel toxins, or crude venoms known to contain them. The majority of detected activities were consistent with predictions, in contrast to poor performance of a number of tested existing predictive methods. Our results provide a framework for comparison of active sites among different functional sub-groups of toxins that will allow a more targeted approach for identification of potential drug leads in the future. PMID:23831284

Malhotra, Anita; Creer, Simon; Harris, John B; Stöcklin, Reto; Favreau, Philippe; Thorpe, Roger S

2013-09-01

66

Familial hiatal hernia in a large five generation family confirming true autosomal dominant inheritance  

PubMed Central

BACKGROUND—Familial hiatal hernia has only rarely been documented.?AIMS—To describe the pattern of inheritance of familial hiatal hernia within an affected family.?SUBJECTS—Thirty eight members of a family pedigree across five generations.?METHODS—All family members were interviewed and investigated by barium meal for evidence of a hiatal hernia.?RESULTS—Twenty three of 38 family members had radiological evidence of a hiatal hernia. No individual with a hiatal hernia was born to unaffected parents. In one case direct male to male transmission was shown.?CONCLUSIONS—Familial inheritance of hiatal hernia does occur. Evidence of direct male to male transmission points to an autosomal dominant mode of inheritance.???Keywords: familial hiatal hernia; Barrett's oesophagus; autosomal dominant genetics PMID:10517898

Carre, I; Johnston, B; Thomas, P; Morrison, P

1999-01-01

67

PATTERN OF CONSANGUINITY AND INBREEDING COEFFICIENT IN SARGODHA DISTRICT, PUNJAB, PAKISTAN.  

PubMed

Summary Consanguinity is widespread in Pakistan. The majority of studies on consanguinity in Pakistan have been carried out in urban metropolitan areas, and data on rural populations are scarce. The present cross-sectional study was conducted in Sargodha district, upper Punjab, Pakistan where the majority of the population reside in rural areas. A random sample of 1800 married females belonging to six tehsils of Sargodha district was obtained and differentials in consanguinity rates and inbreeding coefficient (F) were investigated. The consanguinity rate was calculated to be 56.72% and the inbreeding coefficient was 0.0348. First cousin unions had the highest representation (49.11% of all marriages), and marriages up to distantly related/Biradari constituted 67.94% of all marriages. Among the six tehsils, consanguinity rates ranged from 50.38% in Bhalwal to 62.88% in Sillanwali. A high rate of consanguinity was observed in subjects speaking the Punjabi language, those with self-arranged/arranged-love marriages and those engaged in professional jobs. With respect to the occupation of husbands the highest consanguinity rate was found among landowners (77.59%; F=0.0539) and businessmen (62.62%; F=0.0377). However, consanguinity did not appear to be associated with rural/urban origin or literacy level. The data showed a wide variation in consanguinity rate and inbreeding coefficient across socio-demographic strata in the Sargodha district population. A comparison of Sargodha with other populations of Punjab also showed regional heterogeneity in the pattern of consanguinity, warranting further studies. PMID:25299747

Hina, Saira; Malik, Sajid

2014-10-01

68

Papillon–Lefevre syndrome: Reporting consanguinity as a risk factor  

PubMed Central

Papillon–Lefevre syndrome (PLS) is an autosomal recessive genetic disorder characterized by palmoplantar hyperkeratosis associated with severe early-onset periodontitis and premature loss of primary and permanent teeth. This report describes two cases of PLS in 28-year-old female and 16-year-old male siblings with consanguineously married parents. The patients presented to the Department of Public Health Dentistry of a dental education and research institute in India with thickening, flaking, and scaling of the skin on the palms and soles of the feet. On oral examination, the female patient presented completely resorbed maxillary and mandibular alveolar ridges with retention of only the third molars. The male patient retained only teeth 18, 13, 28, 38, and 45. Based on complete histories and clinical examination findings, a final diagnosis of PLS was made and treatment was initiated using an interdisciplinary dental approach in both cases. PMID:25057233

Shah, Aasim Farooq; Tangade, Pradeep; Agarwal, Swatantra

2014-01-01

69

Large family of quantum weak coin-flipping protocols  

SciTech Connect

Each classical public-coin protocol for coin flipping is naturally associated with a quantum protocol for weak coin flipping. The quantum protocol is obtained by replacing classical randomness with quantum entanglement and by adding a cheat detection test in the last round that verifies the integrity of this entanglement. The set of such protocols defines a family which contains the protocol with bias 0.192 previously found by the author, as well as protocols with bias as low as 1/6 described herein. The family is analyzed by identifying a set of optimal protocols for every number of messages. In the end, tight lower bounds for the bias are obtained which prove that 1/6 is optimal for all protocols within the family.

Mochon, Carlos [Institute for Quantum Information, California Institute of Technology, Pasadena, California 91125 (United States)

2005-08-15

70

[A focus of multiple sclerosis in Bretagne: HLA markers and evaluation of consanguinity].  

PubMed

In a previous study, we established the overall prevalence of multiple sclerosis at 25 per 100,000 inhabitants in the French province of Brittany and found that the geographical distribution was uneven with four circumscribed high prevalence areas with more than 45 per 100,000. We conducted the present study to try to ascertain whether the existence of such clusters of MS could be explained by genetic factors, using two ways: the major histocompatibility markers and the frequency of intermarriage. Among the four areas of high prevalence, we examined the one with the highest prevalence, exempt from migratory movements over the last 100 years. We compared this studied population to a sample of 1005 healthy unrelated individuals coming from all over Brittany, designated as general Brittany population. A large sampling (about 25%) of the population accepted to take part in the study. Regarding HLA markers, we observed in the high prevalence area an increases percentage of B7, B8, B12, DR4 and a decreased percentage of B5, compared with the Brittany control population. The consanguinity coefficient in the population of high MS prevalence area was steadily much higher than the one in neighbouring areas with a low MS prevalence during a long period from 1896 to 1945. Under the reserve of non-randomized sampling of individuals for HLA marker study, our findings yielded a double argument in favor of genetic factors influencing the presence of clusters of MS cases: the particularities of HLA phenotype pattern and the increased consanguinity coefficient. The particularities of HLA polymorphism observed in the high prevalence area are likely to be the consequence of the intermarriage habits of this population. PMID:1962069

Edan, G; Madigand, M; Merienne, M; Morel, G; Sabouraud, O; Salmon, D; Semana, G; Fauchet, R

1991-01-01

71

Hereditary coproporphyria: incidence in a large English family  

Microsoft Academic Search

In a family inheriting the hereditary coproporphyria (HCP) gene, where 414 descendants have been traced through six generations and 135 members screened for faecal porphyrins, 27 subjects were found to have inherited the gene as well as the proband. Seven (six female and one male) in retrospect had probably previously suffered from a clinical attack of porphyria. Enzymological studies were

J Andrews; H Erdjument; D C Nicholson

1984-01-01

72

The first case of CDK5RAP2-related primary microcephaly in a non-consanguineous patient identified by next generation sequencing.  

PubMed

Primary autosomal recessive microcephaly (MCPH) is a genetically heterogeneous condition characterized by congenital microcephaly and intellectual disability. To date, 10 MCPH loci have been identified and due to the genetic heterogeneity of this condition, molecular testing for MCPH can be complicated. Our methods involved employing a next generation sequencing panel of MCPH-related genes allowing for the evaluation of multiple disease loci simultaneously. Next generation sequencing analysis of a 6 year old female with primary microcephaly identified novel compound heterozygous mutations (c.524_528del and c.4005-1G>A) in the CDK5RAP2 gene. A review of the published literature to date reveals that only three mutations have been previously reported in the CDK5RAP2 gene in the homozygous state in three Northern Pakistani and one Somali consanguineous MCPH families. Our patient represents the first non-consanguineous Caucasian individual to have been identified with CDK5RAP2-related MCPH. As only a handful of patients have been reported in the literature with CDK5RAP2-related MCPH, we anticipate the identification of individuals with CDK5RAP2 mutations from all ethnic backgrounds will continue. Our patient contributes to the ethnic and genotypic spectrum of CDK5RAP2-related MCPH and supports the occurrence of this genetic condition beyond that of consanguineous families of certain ethnic populations. Our results also highlight the utility of multi-gene sequencing panels to elucidate the etiology of genetically heterogeneous conditions. PMID:23726037

Tan, Christopher A; Topper, Scott; Ward Melver, Catherine; Stein, Jennifer; Reeder, Amanda; Arndt, Kelly; Das, Soma

2014-04-01

73

Association of cerebral palsy with consanguineous parents and other risk factors in a Palestinian population.  

PubMed

This case-control study investigated risk factors for cerebral palsy in a Palestinian population. Cases were 107 children aged 1-15 years at a cerebral palsy referral centre in Jerusalem; controls were 233 children without cerebral palsy from West Bank outpatient clinics. Data were collected from medical records and a structured questionnaire to parents. In stepwise logistical regression, consanguinity and birth deficits in other family members were positively associated with cerebral palsy (OR = 4.62; 95% CI: 2.07-10.3 and OR = 12.7; 95% CI: 3.13-51.7 respectively), suggesting a possible genetic link. Other risk factors were: perinatal hypoxia (OR = 92.5; 95% CI: 24.5-350), low birth weight (OR = 4.98; 95% CI: 2.01-12.3), twin births (OR = 9.25; 95% CI: 1.29-66.8) and no prenatal medical care (OR = 5.22; 95% CI: 1.18-23.1). This first stepwise model of significant and modifiable risk factors in our population provides useful evidence for policy-makers. PMID:25023773

Daher, S; El-Khairy, L

2014-07-01

74

Broad scan linkage analysis in a large Tourette family pedigree  

SciTech Connect

Attempts to find a gene causing Tourette syndrome (TS) using linkage analysis have been unsuccessful even though as much as 65% of the autosomal genetic map has been excluded by the pooled results from several laboratories collaborating worldwide. One reason for this failure may be the misclassification of affection status of marry-in spouses. Specifically, we have found that six unrelated spouses in our Utah TS pedigree suffer from TS, obsessive-compulsive disorder or chronic motor tics. In light of these findings we decided to conduct a complete genomic scan from this Utah kindred with polymorphic markers in three related sibships in which there was no assortative mating. A linkage study assuming autosomal dominant inheritance was done using tetranucleotide repeat markers developed at the University of Utah. We selected markers that were less than 300 bp in size and that gave a heterozygosity of over 70% upon analysis in 4 CEPH families. Results to date with 95 markers run at an interval of 30 cM (covering 61% of the genome) show no evidence of linkage. We intend to extend the coverage to 100% of the genome. Pending completion of this scan, failure to provide evidence of linkage in our TS pedigree might then be attributed to phenotypic misclassification or erroneous assumptions regarding the genetic model of transmission.

Peiffer, A.; Leppert, M. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States); Wetering, B.J.M. van der [Univ. Hospital Rotterdam (Netherlands)

1994-09-01

75

Malaysia: where big is still better. For Malays, large families are part of the plan.  

PubMed

The benefits of various-sized families in Malaysia were discussed by several women and supplemented with official statements on family planning (FP). The Director of the National Population and Family Development, Dr. Raj Karim, advised that maternal health is jeopardized when women have more than five children. About 30% of reproductive age women in Malaysia have five or more children. A Federation of FP Associations spokesperson agreed that women should be advised of the dangers of bearing over five children, of the importance of spacing births two to four years apart, and of the ideal age of childbearing (21-39 years). The government lacks an official policy on family size. The government position is, however, compatible with Islamic teachings on spacing in order to protect the health of the mother and child. Islamic law does not permit sterilization or abortion. The "fatwas" of Islamic teaching may have been misconstrued by those not using any form of contraception. Dr. Karim, who has five children, reported that having a large family can be difficult for a woman with a job, a career, and a husband or when both parents work. Most Malays desire large families. The average Malay family size was 4.1 children in 1990; Malaysian Chinese have fertility of 2.3 children and Malaysian Indians have 2.6 children. People say that the benefits outweigh the hardships of a large family. PMID:12287219

1993-11-01

76

Models of population-based analyses for data collected from large extended families  

PubMed Central

Large studies of extended families usually collect valuable phenotypic data that may have scientific value for purposes other than testing genetic hypotheses if the families were not selected in a biased manner. These purposes include assessing population-based associations of diseases with risk factors/covariates and estimating population characteristics such as disease prevalence and incidence. Relatedness among participants however, violates the traditional assumption of independent observations in these classic analyses. The commonly used adjustment method for relatedness in population-based analyses is to use marginal models, in which clusters (families) are assumed to be independent (unrelated) with a simple and identical covariance (family) structure such as those called independent, exchangeable and unstructured covariance structures. However, using these simple covariance structures may not be optimally appropriate for outcomes collected from large extended families, and may under- or over-estimate the variances of estimators and thus lead to uncertainty in inferences. Moreover, the assumption that families are unrelated with an identical family structure in a marginal model may not be satisfied for family studies with large extended families. The aim of this paper is to propose models incorporating marginal models approaches with a covariance structure for assessing population-based associations of diseases with their risk factors/covariates and estimating population characteristics for epidemiological studies while adjusting for the complicated relatedness among outcomes (continuous/categorical, normally/non-normally distributed) collected from large extended families. We also discuss theoretical issues of the proposed models and show that the proposed models and covariance structure are appropriate for and capable of achieving the aim. PMID:20882324

Lee, Elisa T.; Howard, Barbara V.; Fabsitz, Richard R.; Devereux, Richard B.; MacCluer, Jean W.; Laston, Sandra; Comuzzie, Anthony G.; Shara, Nawar M.; Welty, Thomas K.

2014-01-01

77

Finnish type of familial amyloidosis: cosegregation of Asp187----Asn mutation of gelsolin with the disease in three large families.  

PubMed Central

Familial amyloidosis of Finnish type (FAF) is one of the familial amyloidotic polyneuropathy (FAP) syndromes, a group of inherited disorders characterized by extracellular accumulation of amyloid and by clinical symptoms and signs of polyneuropathy. FAF, an autosomal dominant trait, belongs to those rare monogenic disorders which occur with increased frequency in the Finnish population: only single FAF cases have been reported from other populations. In most types of FAP syndromes the accumulating protein is a transthyretin variant. However, recent evidence has suggested that the amyloid peptides in FAF are related to gelsolin, an actin modulating protein. The gelsolin fragments isolated from at least one patient with amyloidosis have been reported to have an amino acid substitution, with asparagine replacing aspartic acid at position 187 of the plasma gelsolin. In this study allele-specific oligonucleotides were used to analyze three large FAF families with multiple affected individuals as well as healthy family members. We found the corresponding G-A mutation in nucleotide 654 of the plasma gelsolin gene to cosegregate with the disease. The result was confirmed by sequencing and strongly suggests that the mutation has caused all the FAF cases of these families. Since the disease is clustered in restricted areas on the southern coast of Finland, this mutation most probably causes the majority, if not all, of FAF cases in Finland. Images Figure 2 PMID:1652889

Hiltunen, T; Kiuru, S; Hongell, V; Heliö, T; Palo, J; Peltonen, L

1991-01-01

78

Inbreeding in Gredos mountain range (Spain): contribution of multiple consanguinity and intervalley variation.  

PubMed

The present paper examines consanguineous marriages occurring between 1874 and 1975 in three valleys (Tormes, Alberche, and Tiétar) in the Sierra de Gredos mountain range, Avila province, Spain. Information was obtained from parish registers of 42 localities, corresponding to a total of 41,696 weddings. Consanguineous marriages were defined as those up to the third degree of consanguinity (second cousins). From 1874 to 1975 the percentage of related mates was 4.45% and the inbreeding coefficient was 0.0011868 (for 1874 to 1917 corresponding figures up to the fourth degree were 16.44% and 0.00 19085, respectively). In order to ascertain the characteristics and evolution of mating patterns in Gredos, the contribution of each degree of kinship was analyzed as a whole and then for each valley separately. Regarding total consanguineous marriages in Gredos, there is a low frequency of uncle-niece matings (0.21%) and a first-second cousin mating ratio (C22/C33) of 0.23 (up to the third degree of consanguinity). Before 1918 multiple matings (i.e., those involving more than a single relationship) accounted for 19.16% of consanguineous marriages (up to the fourth degree). The observed frequencies of multiple consanguineous marriages was, on average, about twice that expected at random, and the proportion of such marriages to total inbreeding was 34.65%. The temporal change of the Gredos inbreeding pattern was characterized by a recent decrease; the highest inbreeding levels correspond to the period from 1915 to 1944. Finally, intervalley differences (maximum inbreeding coefficient in the Tormes, minimum in the Tiétar) are interpreted considering the geography, population size, and population mobility for each valley PMID:11446428

Fuster, V; Jiménez, A M; Colantonio, S E

2001-04-01

79

Hereditary coproporphyria: Comparison of molecular and biochemical investigations in a large family  

Microsoft Academic Search

Summary  Hereditary coproporphyria (HCP) is the least common of the three autosomal dominant acute porphyrias. To compare the sensitivity\\u000a of metabolite measurements for the identification of asymptomatic HCP, we carried out a molecular and biochemical investigation\\u000a of a large family in which HCP is caused by a previously unreported frameshift mutation (c.119delA). Thirteen of 19 asymptomatic\\u000a family members, aged 10–72 years,

K. R. Allen; S. D. Whatley; T. J. Degg; J. H. Barth

2005-01-01

80

Predicting specificity-determining residues in two large eukaryotic transcription factor families  

PubMed Central

Certain amino acid residues in a protein, when mutated, change the protein's function. We present an improved method of finding these specificity-determining positions that uses all the protein sequence data available for a family of homologous proteins. We study in detail two families of eukaryotic transcription factors, basic leucine zippers and nuclear receptors, because of the large amount of sequences and experimental data available. These protein families also have a clear definition of functional specificity: DNA-binding specificity. We compare our results to three other methods, including the evolutionary trace algorithm and a method that depends on orthology relationships. All of the predictions are compared to the available mutational and crystallographic data. We find that our method provides superior predictions of the known specificity-determining residues and also predicts residue positions within these families that deserve further study for their roles in functional specificity. PMID:16085755

Donald, Jason E.; Shakhnovich, Eugene I.

2005-01-01

81

Large Families of Asymptotically Optimal Two-Dimensional Optical Orthogonal Codes  

E-print Network

1 Large Families of Asymptotically Optimal Two-Dimensional Optical Orthogonal Codes Reza Omrani codes are provided. Index Terms--Optical orthogonal codes, optical CDMA, OCDMA, two-dimensional codes, 2 two-dimensional optical orthogonal codes (2-D OOCs) that spread in both time and wavelength domain

Gesbert, David

82

A Large Multiple Endocrine Neoplasia Type 1 Family with Clinical Expression Suggestive of Anticipation  

Microsoft Academic Search

We describe a large multigenerational multiple endocrine neopla- sia Type 1 (MEN1) family with clinical expression suggestive of an- ticipation. In the second and third generations, two deceased obligate gene carriers died at the ages of 85 and 76 without the history of MEN1, whereas two other living gene carriers above the age of 65 have had no clinical evidence

SOPHIE GIRAUD; HELENE CHOPLIN; BIN TEAN TEH; JAMES LESPINASSE; ANNE JOUVET; FRANCOISE LABAT-MOLEUR; GILBERT LENOIR; BEATRICE HAMON; PATRICK HAMON; ALAIN CALENDER

2010-01-01

83

Identification of a novel FBN1 gene mutation in a large Pakistani family with Marfan syndrome  

PubMed Central

Purpose To describe a novel mutation in the fibrillin-1 (FBN1) gene in a large Pakistani family with autosomal dominant Marfan syndrome (MFS). Methods Blood samples were collected of 11 family members affected with Marfan syndrome, and DNA was isolated by phenol-extraction. The coding exons of FBN1 were analyzed by polymerase chain reaction (PCR) and direct sequencing. One hundred-thirty controls were screened for a mutation in the FBN1 gene that was identified in this family by restriction fragment length polymorphism (RFLP) analysis. Results A novel heterozygous missense mutation c.2368T>A; p.Cys790Ser was observed in exon 19. This mutation substitutes a highly conserved cysteine residue by serine in a calcium binding epidermal growth factor-like domain (cbEGF) of FBN1. This mutation was present in all affected members and absent from unaffected individuals of the family in addition to 130 healthy Pakistani controls. Interestingly all affected family members presented with ectopia lentis, myopia and glaucoma, but lacked the cardinal cardiovascular features of MFS. Conclusions This is a first report of a mutation in FBN1 in MFS patients of Pakistani origin. The identification of a FBN1 mutation in this family confirms the diagnosis of MFS patients and expands the worldwide spectrum of FBN1 mutations. PMID:22876116

Micheal, Shazia; Khan, Muhammad Imran; Akhtar, Farah; Weiss, Marjan M.; Islam, Farah; Ali, Mehmood; Qamar, Raheel; Maugeri, Alessandra

2012-01-01

84

Genetic heterogeneity in psoriasis vulgaris based on linkage analyses of a large family material  

SciTech Connect

Information on psoriasis among parents and siblings in 14,008 families has been collected. On the basis of this material, evidence for monogenetic autosomal recessive inheritance of psoriasis has recently been presented. Indications from more than one type of non-pustular psoriasis has been obtained from the population genetic data. Molecular genetic linkage analysis of psoriasis to a number of polymorphic genetic markers for a large number of families has been made. It is apparent that there is genetic heterogeneity in a psoriasis population with regard to psoriasis genes. Using the computer program Linkage 5.0 and a formula for heterogeneity, a lodscore over 3.0 for one locus has been obtained. This locus has further been confirmed by several other markers in the vicinity. The locus found is linked to slightly over half of the families, indicating that there are more genetically independent types of psoriasis. The age at onset of those families that are apparently linked to this locus have a slightly higher age at onset than those not linked to that locus but with a considerable overlap. In spite of close coverage of the whole chromosomes number 6 and 17, no linkage has been found in this regions. This indicates that neither the HLA region nor the region earlier found to be involved in one family with psoriasis are primarily involved in our families.

Wahlstroem, J.; Swanbeck, G.; Inerot, A. [ Univ. of Goeteborg (Sweden)] [and others

1994-09-01

85

Large, rapidly evolving gene families are at the forefront of host-parasite interactions in Apicomplexa.  

PubMed

SUMMARY The Apicomplexa is a phylum of parasitic protozoa, which includes the malaria parasite Plasmodium, amongst other species that can devastate human and animal health. The past decade has seen the release of genome sequences for many of the most important apicomplexan species, providing an excellent basis for improving our understanding of their biology. One of the key features of each genome is a unique set of large, variant gene families. Although closely related species share the same families, even different types of malaria parasite have distinct families. In some species they tend to be found at the ends of chromosomes, which may facilitate aspects of gene expression regulation and generation of sequence diversity. In others they are scattered apparently randomly across chromosomes. For some families there is evidence they are involved in antigenic variation, immune regulation and immune evasion. For others there are no known functions. Even where function is unknown these families are most often predicted to be exposed to the host, contain much sequence diversity and evolve rapidly. Based on these properties it is clear that they are at the forefront of host-parasite interactions. In this review I compare and contrast the genomic context, gene structure, gene expression, protein localization and function of these families across different species. PMID:25257746

Reid, Adam J

2015-02-01

86

Structural, functional, and evolutionary analysis of the unusually large stilbene synthase gene family in grapevine.  

PubMed

Stilbenes are a small family of phenylpropanoids produced in a number of unrelated plant species, including grapevine (Vitis vinifera). In addition to their participation in defense mechanisms in plants, stilbenes, such as resveratrol, display important pharmacological properties and are postulated to be involved in the health benefits associated with a moderate consumption of red wine. Stilbene synthases (STSs), which catalyze the biosynthesis of the stilbene backbone, seem to have evolved from chalcone synthases (CHSs) several times independently in stilbene-producing plants. STS genes usually form small families of two to five closely related paralogs. By contrast, the sequence of grapevine reference genome (cv PN40024) has revealed an unusually large STS gene family. Here, we combine molecular evolution and structural and functional analyses to investigate further the high number of STS genes in grapevine. Our reannotation of the STS and CHS gene families yielded 48 STS genes, including at least 32 potentially functional ones. Functional characterization of nine genes representing most of the STS gene family diversity clearly indicated that these genes do encode for proteins with STS activity. Evolutionary analysis of the STS gene family revealed that both STS and CHS evolution are dominated by purifying selection, with no evidence for strong selection for new functions among STS genes. However, we found a few sites under different selection pressures in CHS and STS sequences, whose potential functional consequences are discussed using a structural model of a typical STS from grapevine that we developed. PMID:22961129

Parage, Claire; Tavares, Raquel; Réty, Stéphane; Baltenweck-Guyot, Raymonde; Poutaraud, Anne; Renault, Lauriane; Heintz, Dimitri; Lugan, Raphaël; Marais, Gabriel A B; Aubourg, Sébastien; Hugueney, Philippe

2012-11-01

87

Phenotype-Genotype Correlation in Wilson Disease in a Large Lebanese Family: Association of c.2299insC with Hepatic and of p. Ala1003Thr with Neurologic Phenotype  

PubMed Central

Genotype phenotype correlations in Wilson disease (WD) are best established in homozygous patients or in compound heterozygous patients carrying the same set of mutations. We determined the clinical phenotype of patients with WD carrying the c.2298_2299insC in Exon 8 (c.2299insC) or the p. Ala1003Thr missense substitution in Exon 13 mutations in the homozygous or compound heterozygous state. We investigated 76 members of a single large Lebanese family. Their genotypes were determined, and clinical assessments were carried out for affected subjects. We also performed a literature search retrieving the phenotypes of patients carrying the same mutations of our patients in the homozygous or compound heterozygous state. There were 7 consanguineous marriages in this family and the prevalence of WD was 8.9% and of carriers of ATP7B mutation 44.7%. WD was confirmed in 9 out of 76 subjects. All 9 had the c.2299insC mutation, 5 homozygous and 4-compound heterozygous with p. Ala1003Thr. Six of our patients had hepatic, 2 had neurologic and 1 had asymptomatic phenotype. Based on our data and a literature review, clear phenotypes were reported for 38 patients worldwide carrying the c.2299insC mutation. About 53% of those have hepatic and 29% have neurologic phenotype. Furthermore, there were 10 compound heterozygous patients carrying the p. Ala1003Thr mutation. Among those, 80% having c.2299insC as the second mutation had hepatic phenotype, and all others had neurologic phenotype. We hereby report an association between the c.2299insC mutation and hepatic phenotype and between the p. Ala1003Thr mutation and neurologic phenotype. PMID:25390358

Usta, Julnar; Wehbeh, Antonios; Rida, Khaled; El-Rifai, Omar; Estiphan, Theresa Alicia; Majarian, Tamar; Barada, Kassem

2014-01-01

88

The influence of admixture and consanguinity on population genetic diversity in Middle East.  

PubMed

The Middle East (ME) is an important crossroad where modern humans migrated 'out of Africa' and spread into Europe and Asia. After the initial peopling and long-term isolation leading to well-differentiated populations, the ME also had a crucial role in subsequent human migrations among Africa, Europe and Asia; thus, recent population admixture has been common in the ME. On the other hand, consanguinity, a well-known practice in the ME, often reduces genetic diversity and works in opposition to admixture. Here, we explored the degree to which admixture and consanguinity jointly affected genetic diversity in ME populations. Genome-wide single-nucleotide polymorphism data were generated in two representative ME populations (Arabian and Iranian), with comparisons made with populations worldwide. Our results revealed an overall higher genetic diversity in both ME populations relative to other non-African populations. We identified a much larger number of long runs of homozygosity in ME populations than in any other populations, which was most likely attributed to high levels of consanguineous marriages that significantly decreased both individual and population heterozygosity. Additionally, we were able to distinguish African, European and Asian ancestries in ME populations and quantify the impact of admixture and consanguinity with statistical approaches. Interestingly, genomic regions with significantly excessive ancestry from individual source populations are functionally enriched in olfactory pathways, which were suspected to be under natural selection. Our findings suggest that genetic admixture, consanguinity and natural selection have collectively shaped the genetic diversity of ME populations, which has important implications in both evolutionary studies and medical practices. PMID:25253659

Yang, Xiong; Al-Bustan, Suzanne; Feng, Qidi; Guo, Wei; Ma, Zhiming; Marafie, Makia; Jacob, Sindhu; Al-Mulla, Fahd; Xu, Shuhua

2014-11-01

89

Clinical and linkage study of a large family with simple ectopia lentis linked to FBN1  

SciTech Connect

Simple ectopia lentis (EL) was studied in a large family, by clinical examination and analysis of linkage to markers in the region of FBN1, the gene for fibrillin which causes Marfan syndrome on chromosome 15. No patient had clinical or echocardiographic evidence of Marfan syndrome, although there was a trend towards relatively longer measurements of height; lower segment; arm span; middle finger, hand, and foot length in the affected members of the family, compared with unaffected sibs of the same sex. Analysis of linkage to intragenic FBN1 markers was inconclusive because they were relatively uninformative. Construction of a multipoint background map from the CEPH reference families identified microsatellite markers linked closely to FBN1 which could demonstrate linkage of EL in this family to the FBN1 region. LINKMAP analysis detected a multipoint lod score of 5.68 at D15S119, a marker approximately 6 cM distal to FBN1, and a multipoint lod score of 5.04 at FBN1. The EL gene in this family is likely to be allelic to Marfan syndrome, and molecular characterization of the FBN1 mutation should now be possible. 25 refs., 6 figs., 2 tabs.

Edwards, M.J.; Roberts, J.; Partington, M.W. [Newcastle and Northern New South Wales Genetics Service (Australia); Colley, P.W. [John Hunter Hospital, Newcastle (Australia); Hollway, G.E.; Kozman, H.M.; Mulley, J.C. [Adelaide Children`s Hospital, North Adelaide (Australia)

1994-10-15

90

Identification of a new locus for autosomal dominant non-syndromic hearing impairment (DFNA7) in a large Norwegian family  

Microsoft Academic Search

Hereditary hearing impairment affects about 1 in 1000 newborns. In most cases hearing loss is non-syndromic with no other clinical features, while in other families deafness is associated with specific clinical abnormalities. Analysis of large families with non-syndromic and syndromic deafness have been used to identify genes or gene locations that cause hearing impairment. The present report describes a large

T. Fagerheim; Ø. Nilssen; P. Raeymaekers; V. Brox; T. Moum; H. H. Elverland; E. Teig; H. H. Omland; G. K. Fostad; L. Tranebjærg

1996-01-01

91

Frequent detection of parental consanguinity in children with developmental disorders by a combined CGH and SNP microarray  

PubMed Central

Background Genomic microarrays have been used as the first-tier cytogenetic diagnostic test for patients with developmental delay/intellectual disability, autism spectrum disorders and/or multiple congenital anomalies. The use of SNP arrays has revealed regions of homozygosity in the genome which can lead to identification of uniparental disomy and parental consanguinity in addition to copy number variations. Consanguinity is associated with an increased risk of birth defects and autosomal recessive disorders. However, the frequency of parental consanguinity in children with developmental disabilities is unknown, and consanguineous couples may not be identified during doctor’s visit or genetic counseling without microarray. Results We studied 607 proband pediatric patients referred for developmental disorders using a 4?×?180 K array containing both CGH and SNP probes. Using 720, 360, 180, and 90 Mb as the expected sizes of homozygosity for an estimated coefficient of inbreeding (F) 1/4, 1/8, 1/16, 1/32, parental consanguinity was detected in 21cases (3.46%). Conclusion Parental consanguinity is not uncommon in children with developmental problems in our study population, and can be identified by use of a combined CGH and SNP chromosome microarray. Identification of parental consanguinity in such cases can be important for further diagnostic testing. PMID:24053112

2013-01-01

92

Hereditary coproporphyria: comparison of molecular and biochemical investigations in a large family.  

PubMed

Hereditary coproporphyria (HCP) is the least common of the three autosomal dominant acute porphyrias. To compare the sensitivity of metabolite measurements for the identification of asymptomatic HCP, we carried out a molecular and biochemical investigation of a large family in which HCP is caused by a previously unreported frameshift mutation (c.119delA). Thirteen of 19 asymptomatic family members, aged 10-72 years, were shown by mutational analysis to have HCP. The faecal coproporphyrin isomer III:I ratio was increased in all of these 13 family members; faecal total porphyrin concentration and urinary porphyrin excretion were increased in 11 and 8 of them, respectively. Plasma porphyrin concentrations were marginally increased in three individuals and plasma fluorescence emission scanning showed a porphyrin peak at 618 nm in two of these. Our results add to the evidence that an increased faecal porphyrin coproporphyrin III:I ratio is a highly sensitive test for the detection of clinically latent HCP in individuals over the age of 10 years; its sensitivity below this age remains uncertain. They also show that plasma fluorescence emission scanning is not useful for the investigation of families with HCP. PMID:16151909

Allen, K R; Whatley, S D; Degg, T J; Barth, J H

2005-01-01

93

Towards identification of an epilepsy gene in a large family with idiopathic generalized epilepsy  

SciTech Connect

To identify the disease gene in a large, multiplex family segregating an autosomal dominant form of idiopathic generalized epilepsy (IGE). The IGEs have been recognized for several decades as being genetically determined. However, large pedigrees with a clear Mendelian inheritance are not commonly available. This, and the presence of locus heterogeneity have been obstacles to the identification of linkage in several IGE syndromes. We have identified a large IGE kindred with fifty-eight living individuals, including 26 affecteds, showing a clear autosomal dominant inheritance with incomplete penetrance. Forty-fur informative individuals, including 23 affecteds, were selected for the linkage studies. We have chosen 200 polymorphic microsatellite markers, about 20 cM apart, throughout the human autosomes as a genome-search linkage strategy. To date, 47 markers, representing 30% of the human genome, have been excluded for linkage in the Australian kindred. As our study progresses, we will report up-to-date results.

Roussear, M.; Lopes-Cendes, I. [Montreal General Hospital, Quebec (Canada); Berkovic, S.F. [Austin Hospital, Melbourne (Australia)] [and others

1994-09-01

94

Characteristics of Women in Consanguineous Marriages in Egypt, 1988–2000  

Microsoft Academic Search

This article reviews three mechanisms related to autonomy, wealth, and local cultural factors, which are said to underly the\\u000a high prevalence of consanguineous marriage in Arab societies. It then assesses each of them empirically in two stages. The\\u000a first uses a pooled dataset constituted by the most recent marriage cohorts in the 1992 and 2000 waves of the Egyptian Demographic

Alexander A. Weinreb

2008-01-01

95

Penetrance and clinical consequences of a gross SDHB deletion in a large family.  

PubMed

Mutations in the gene encoding subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) are inherited in an autosomal dominant manner and are associated with hereditary paraganglioma (PGL) and pheochromocytoma. The phenotype of patients with SDHB point mutations has been previously described. However, the phenotype and penetrance of gross SDHB deletions have not been well characterized as they are rarely described. The objective was to describe the phenotype and estimate the penetrance of an exon 1 large SDHB deletion in one kindred. A retrospective and prospective study of 41 relatives across five generations was carried out. The main outcome measures were genetic testing, clinical presentations, plasma catecholamines and their O-methylated metabolites. Of the 41 mutation carriers identified, 11 were diagnosed with PGL, 12 were found to be healthy carriers after evaluation, and 18 were reportedly healthy based on family history accounts. The penetrance of PGL related to the exon 1 large SDHB deletion in this family was estimated to be 35% by age 40. Variable expressivity of the phenotype associated with a large exon 1 SDHB deletion was observed, including low penetrance, diverse primary PGL tumor locations, and malignant potential. PMID:19389109

Solis, D C; Burnichon, N; Timmers, H J L M; Raygada, M J; Kozupa, A; Merino, M J; Makey, D; Adams, K T; Venisse, A; Gimenez-Roqueplo, A-P; Pacak, K

2009-04-01

96

[Analysis of consanguinity in some populations of the V Region, Valparaiso, Chile, from 1880 to 1969].  

PubMed

The population structure of 10 populations ("comunas") in Valparaíso, V Region Chile, was studied through the frequency of consanguineous marriages (%CM) and the coefficient of consanguinity (alpha), in order to know their dynamics, and gather information for clinical and genetic epidemiological studies as well as for isonymy studies. The comunas were grouped according to density: Group I, high density, more than 100 inhabitants/km2; Group II, intermediate, between 25 and 99 inhabitants/km2; and Group III, low, less than 25 inhabitants/km2. Data were obtained from parochial archives and national census, from 1880 to 1969. CM's were divided in: uncle-aunt/nephew-niece (12), first cousins (22), first cousins one removed (23), second cousins (33) and multiple consanguinity (M), and the four subtypes of 12 and 22. Percentage of CM and alpha diminish in time. Groups I and II show similar values, but lower in I, and show a constant decrease. Group III has higher values and considerable fluactuations. Types 12 and 22 contribute mostly to %CM and alpha in the 3 groups. Subtypes of 12 and 22 do not occur at random. This temporary and spatial behavior can be explained because of sociocultural and socioeconomical factors in each group, being density an indicator of endogamy. This behavior is consistent with current coefficients of endogamy obtained by isonymy. PMID:9334449

Lazo, B; Campusano, C; Pinto-Cisternas, J

1996-01-01

97

Autosomal dominant brachyolmia in a large Swedish family: phenotypic spectrum and natural course.  

PubMed

Autosomal dominant brachyolmia (Type 3, OMIM #113500) belongs to a group of skeletal dysplasias caused by mutations in the transient receptor potential cation channel, subfamily V, member 4 (TRPV4) gene, encoding a Ca++-permeable, non-selective cation channel. The disorder is characterized by disproportionate short stature with short trunk, scoliosis and platyspondyly. The phenotypic variability and long-term natural course remain inadequately characterized. The purpose of this study was to describe a large Swedish family with brachyolmia type 3 due to a heterozygous TRPV4 mutation c.1847G>A (p.R616Q) in 11 individuals. The mutation has previously been detected in another family with autosomal dominant brachyolmia [Rock et al., 2008]. Review of hospital records and patient assessments indicated that clinical symptoms of brachyolmia became evident by school age with chronic pain in the spine and hips; radiographic changes were evident earlier. Growth was not affected during early childhood but deteriorated with age in some patients due to increasing spinal involvement. Affected individuals had a wide range of subjective symptoms with chronic pain in the extremities and the spine, and paresthesias. Our findings indicate that autosomal dominant brachyolmia may be associated with significant long-term morbidity, as seen in this family. PMID:24677493

Grigelioniene, Giedre; Geiberger, Stefan; Horemuzova, Eva; Moström, Eva; Jäntti, Nina; Neumeyer, Lo; Åström, Eva; Nordenskjöld, Magnus; Nordgren, Ann; Mäkitie, Outi

2014-07-01

98

Ocular and craniofacial phenotypes in a large Brazilian family with congenital aniridia.  

PubMed

Congenital aniridia is a rare genetic disorder characterized by varying degrees of iris hypoplasia that are associated with additional ocular abnormalities. More than 90% of the causal mutations identified are found in the PAX6 gene, a transcription factor of critical importance in the process of neurogenesis and ocular development. Here, we investigate clinical, molecular, and craniofacial features of a large Brazilian family with congenital aniridia. Among the 56 eyes evaluated, phenotype variation encompassed bilateral total aniridia to mild iris defects with extensive variation between eyes of the same individual. PAX6 molecular screening indicated a heterozygous splice mutation (c.141?+?1G>A). Thus, we hypothesize that this splicing event may cause variation in the expression of the wild-type transcript, which may lead to the observed variation in phenotype. Affected individuals were more brachycephalic, even though their face height and cephalic circumference were not significantly different when compared to those of non-affected relatives. From this, we infer that the head shape of affected subjects may also be a result of the PAX6 splice-site mutation. Our data summarize the clinical variability associated with the ocular phenotype in a large family with aniridia, and help shed light on the role of PAX6 in neurocranial development. PMID:24266705

Fernandes-Lima, Z S; Paixão-Côrtes, V R; de Andrade, A K M; Fernandes, A S; Coronado, B N L; Monte Filho, H P; Santos, M J; de Omena Filho, R L; Biondi, F C; Ruiz-Linares, A; Ramallo, V; Hünemeier, T; Schuler-Faccini, L; Monlleó, I L

2015-01-01

99

A large and functionally diverse family of Fad2 genes in safflower (Carthamus tinctorius L.)  

PubMed Central

Background The application and nutritional value of vegetable oil is highly dependent on its fatty acid composition, especially the relative proportion of its two major fatty acids, i.e oleic acid and linoleic acid. Microsomal oleoyl phosphatidylcholine desaturase encoded by FAD2 gene is known to introduce a double bond at the ?12 position of an oleic acid on phosphatidylcholine and convert it to linoleic acid. The known plant FAD2 enzymes are encoded by small gene families consisting of 1-4 members. In addition to the classic oleate ?12-desaturation activity, functional variants of FAD2 that are capable of undertaking additional or alternative acyl modifications have also been reported in a limited number of plant species. In this study, our objective was to identify FAD2 genes from safflower and analyse their differential expression profile and potentially diversified functionality. Results We report here the characterization and functional expression of an exceptionally large FAD2 gene family from safflower, and the temporal and spatial expression profiles of these genes as revealed through Real-Time quantitative PCR. The diversified functionalities of some of the safflower FAD2 gene family members were demonstrated by ectopic expression in yeast and transient expression in Nicotiana benthamiana leaves. CtFAD2-1 and CtFAD2-10 were demonstrated to be oleate desaturases specifically expressed in developing seeds and flower head, respectively, while CtFAD2-2 appears to have relatively low oleate desaturation activity throughout the plant. CtFAD2-5 and CtFAD2-8 are specifically expressed in root tissues, while CtFAD2-3, 4, 6, 7 are mostly expressed in the cotyledons and hypocotyls in young safflower seedlings. CtFAD2-9 was found to encode a novel desaturase operating on C16:1 substrate. CtFAD2-11 is a tri-functional enzyme able to introduce a carbon double bond in either cis or trans configuration, or a carbon triple (acetylenic) bond at the ?12 position. Conclusions In this study, we isolated an unusually large FAD2 gene family with 11 members from safflower. The seed expressed FAD2 oleate ?12 desaturase genes identified in this study will provide candidate targets to manipulate the oleic acid level in safflower seed oil. Further, the divergent FAD2 enzymes with novel functionality could be used to produce rare fatty acids, such as crepenynic acid, in genetically engineered crop plants that are precursors for economically important phytoalexins and oleochemical products. PMID:23289946

2013-01-01

100

Germline BHD-Mutation Spectrum and Phenotype Analysis of a Large Cohort of Families with Birt-Hogg-Dubé Syndrome  

PubMed Central

Birt-Hogg-Dubé syndrome (BHD), a genodermatosis characterized by multiple hamartomas of the hair follicle (fibrofolliculoma), predisposes individuals to an increased risk of developing renal neoplasms and spontaneous pneumothorax. Previously, we localized the BHD locus (also known as FLCN) to chromosome 17p11.2 by linkage analysis and subsequently identified germline mutations in a novel gene in probands from eight of the nine families with BHD in our screening panel. Affected members of five of the families inherited an insertion/deletion of a cytosine in a C8 tract in exon 11. This mutation was also identified by exon 11 screening in probands from 22 of 52 additional families with BHD and therefore represents a hypermutable “hotspot” for mutation in BHD. Here, we screened the remaining 30 families from this large BHD cohort by direct sequence analysis and identified germline BHD mutations in 84% (51/61) of all families with BHD recruited to our study. Mutations were located along the entire length of the coding region, including 16 insertion/deletion, 3 nonsense, and 3 splice-site mutations. The majority of BHD mutations were predicted to truncate the BHD protein, folliculin. Among patients with a mutation in the exon 11 hotspot, significantly fewer renal tumors were observed in patients with the C-deletion than those with the C-insertion mutation. Coding-sequence mutations were not found, however, in probands from two large families with BHD whose affected members shared their family’s BHD-affected haplotype. Of the 53 families with BHD whose members inherited either a germline mutation or the affected haplotype, 24 (45%) had at least one member with renal neoplasms. Three families classified with familial renal oncocytoma were identified with BHD mutations, which represents the first disease gene associated with this rare form of renal neoplasm. This study expands the BHD-mutation spectrum and evaluates genotype-phenotype correlations among families with BHD. PMID:15852235

Schmidt, Laura S.; Nickerson, Michael L.; Warren, Michelle B.; Glenn, Gladys M.; Toro, Jorge R.; Merino, Maria J.; Turner, Maria L.; Choyke, Peter L.; Sharma, Nirmala; Peterson, James; Morrison, Patrick; Maher, Eamonn R.; Walther, McClellan M.; Zbar, Berton; Linehan, W. Marston

2005-01-01

101

Identification of a FUS splicing mutation in a large family with amyotrophic lateral sclerosis.  

PubMed

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. Genetic studies have led, thus far, to the identification of 12 loci and 9 genes for familial ALS (FALS). Although the distribution and impact of superoxide dismutase 1 mutations has been extensively examined for over a decade, the recently identified FALS-associated FUS gene has been less studied. Therefore, we set out to screen our collection of FALS cases for FUS mutations. All 15 exons of FUS were amplified and sequenced in 154 unrelated FALS cases and 475 ethnically matched healthy individuals. One substitution located in the acceptor splice site of intron 14 was identified in all affected members of a large family, causing the skipping of the last 13 amino acids of the protein and the translation of 7 novel amino acids, resulting from the new translation of a part of the 3' untranslated region. Our study identified a new splicing mutation in the highly conserved C-terminal of the FUS protein. Thus far most FUS mutations are missenses, and our findings, combined with those of others, confirm the importance of the C-terminal portion of the protein, adding additional support for FUS mutations having a critical role in ALS. PMID:21160488

Belzil, Véronique V; St-Onge, Judith; Daoud, Hussein; Desjarlais, Anne; Bouchard, Jean-Pierre; Dupré, Nicolas; Camu, William; Dion, Patrick A; Rouleau, Guy A

2011-03-01

102

Segregation of FRAXE in a large family: Clinical, psychometric, cytogenetic, and molecular data  

SciTech Connect

During an ongoing study on X-linked mental retardation, we ascertained a large family in which mild mental retardation was cosegregating with a fragile site at Xq27-28. Clinical, psychometric, cytogenetic, and molecular studies were performed. Apart from mild mental retardation, affected males and females did not show a specific clinical phenotype. Psychometric assessment of four representative affected individuals revealed low academic achievements, with verbal and performance IQs of 61-75 and 70-82, respectively. Cytogenetically the fragile site was always present in affected males and was not always present in affected females. With FISH the fragile site was located within the FRAXE region. The expanded GCC repeat of FRAXE was seen in affected males and females either as a discrete band or as a broad smear. No expansion was seen in unaffected males, whereas three unaffected females did have an enlarged GCC repeat. Maternal transmission of FRAXE may lead to expansion or contraction of the GCC repeat length, whereas in all cases of paternal transmission contraction was seen. In striking contrast to the situation in fragile X syndrome, affected males may have affected daughters. In addition, there appears to be no premutation of the FRAXE GCC repeat, since in the family studied here all males lacking the normal allele were found to be affected. 41 refs., 4 figs., 5 tabs.

Hamel, B.C.J.; Smits, A.P.T.; Smeets, F.C.M.; Schoute, F.; Assman-Hulsmans, C.F.C.H. [Univ. Hospital, Nijmegen (Netherlands); Graaff, E. de; Eussen, B.H.J.; Oostra, B.A. [Erasmus Univ., Rotterdam (Netherlands); Knight, S.J.L. [John Radcliffe Hospital, Headington, Oxford (Canada)

1994-11-01

103

Multicentric Castleman Disease in an HHV8-Infected Child Born to Consanguineous Parents With Systematic Review  

PubMed Central

Childhood multicentric Castleman disease (MCD) is a rare and unexplained lymphoproliferative disorder. We report a human herpesvirus-8 (HHV-8)-infected child, born to consanguineous Comorian parents, who displayed isolated MCD in the absence of any known immunodeficiency. We also systematically review the clinical features of the 32 children previously reported with isolated and unexplained MCD. The characteristics of this patient and the geographic areas of origin of most previous cases suggest that pediatric MCD is associated with HHV-8 infection. Moreover, as previously suggested for Kaposi sarcoma, MCD in childhood may result from inborn errors of immunity to HHV-8 infection. PMID:22157133

Moshous, Despina; Cassar, Olivier; Reguerre, Yves; Byun, Minji; Pedergnana, Vincent; Canioni, Danielle; Gessain, Antoine; Oksenhendler, Eric; Fieschi, Claire; Mahlaoui, Nizar; Rivière, Jean-Pierre; Herbigneaux, Rose-Marie; Muszlak, Matthias; Arnaud, Jean-Pierre; Fischer, Alain; Picard, Capucine; Blanche, Stéphane; Plancoulaine, Sabine

2012-01-01

104

Exclusion of linkage to chromosome 14q in a large South Tyrolean family with Idiopathic Basal Ganglia Calcification (IBGC).  

PubMed

Familial Idiopathic Basal Ganglia Calcification (FIBGC) is a neurodegenerative syndrome that usually follows an autosomal dominant pattern of inheritance. Linkage to only one locus on chromosome 14q (IBCG1) has been described so far. We identified and characterized a large multigenerational Italian family from a population isolate with 14 FIBGC affected members. Linkage analysis excluded the IBCG1 locus, thus demonstrating further locus heterogeneity for this disease. PMID:18361429

Volpato, Claudia Béu; De Grandi, Alessandro; Buffone, Ebba; Pichler, Irene; Gebert, Uwe; Schifferle, Günther; Schönhuber, Rudolf; Pramstaller, Peter P

2008-10-01

105

Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families  

Microsoft Academic Search

BACKGROUND: BRCA1 and BRCA2 are the two most important genes associated with familial breast and ovarian cancer susceptibility. In addition, PALB2 has recently been identified as a breast cancer susceptibility gene in several populations. Here we have evaluated whether large genomic rearrangement in these genes could explain some of Finnish breast and\\/or ovarian cancer families. METHODS: Altogether 61 index patients

Katri Pylkäs; Hannele Erkko; Jenni Nikkilä; Szilvia Sólyom; Robert Winqvist

2008-01-01

106

Coexistence of multiple endocrine neoplasia type 1 and type 2 in a large Italian family.  

PubMed

To describe the coexistence of mutations of both the multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) genes in a large Italian family and evaluate if it could be associated with more aggressive clinical manifestations of the two syndromes. Blood samples were obtained for genetic and biochemical analyses. The RET gene exons (8, 10, 11, 13, 14, 15, 16, 18) and the MEN1 coding regions, including the exon-intron boundaries, were amplified by PCR and directly sequenced. We identified two germline mutations in the proband: the first one, K666M, located at the exon 11 of RET proto-oncogene and the second one, IVS4+1G>T, located in the MEN1 gene. The functional characterization of IVS4+1G>T variation, located in the splicing donor site of exon 4 of MEN1 gene, caused the in-frame junction of exon 3 to exon 5, thus obtaining a shorter protein. The same proband's germline mutations were found in 16 relatives out of 21 screened subjects: 8 carried IVS4+1G>T, 4 RET K666M, and 4 both the mutations. This is the second report in literature of coexistence in the same family of germline mutations of both RET proto-oncogene and MEN1 gene. The simultaneous presence of the two mutations was not apparently associated with more aggressive diseases, since at last follow-up all patients appeared to be disease-free or well compensated by medical therapy; finally, no one exhibited metastatic diseases. PMID:21678021

Mastroianno, Sandra; Torlontano, Massimo; Scillitani, Alfredo; D'Aloiso, Leonardo; Verrienti, Antonella; Bonfitto, Nazario; De Bonis, Antonio; D'Agruma, Leonardo; Muscarella, Lucia Anna; Guarnieri, Vito; Dicembrino, Franca; Maranghi, Marianna; Durante, Cosimo; Filetti, Sebastiano

2011-12-01

107

Large, rapidly evolving intergenic spacers in the mitochondrial DNA of the salamander family Ambystomatidae (Amphibia: Caudata).  

PubMed

We report the presence, in the mitochondrial DNA (mtDNA) of all of the sexual species of the salamander family Ambystomatidae, of a shared 240-bp intergenic spacer between tRNAThr and tRNAPro. We place the intergenic spacer in context by presenting the sequence of 1,746 bp of mtDNA from Ambystoma tigrinum tigrinum, describe the nucleotide composition of the intergenic spacer in all of the species of Ambystomatidae, and compare it to other coding and noncoding regions of Ambystoma and several other vertebrate mtDNAs. The nucleotide substitution rate of the intergenic spacer is approximately three times faster than the substitution rate of the control region, as shown by comparisons among six Ambystoma macrodactylum sequences and eight members of the Ambystoma tigrinum complex. We also found additional inserts within the intergenic spacers of five species that varied from 87-444 bp in length. The presence of the intergenic spacer in all sexual species of Ambystomatidae suggests that it arose at least 20 MYA and has been a stable component of the ambystomatid mtDNA ever since. As such, it represents one of the few examples of a large and persistent intergenic spacer in the mtDNA of any vertebrate clade. PMID:9364774

McKnight, M L; Shaffer, H B

1997-11-01

108

Functional heterogeneity of a large family of human LTR-like promoters and enhancers.  

PubMed Central

The human genome contains a variety of elements similar in structure to retroviruses and retrotransposons. We have shown that the long terminal repeat (LTR) sequences of a large family of human retrovirus-like elements, RTVL-H, are heterogeneous in their ability to regulate the expression of linked genes. Although all of five LTRs tested could promote expression of the chloramphenicol acetyltransferase (CAT) gene, their relative promoter activities as well as range of activities varied widely. Several of the LTRs tested also exhibited bidirectional promoter activity either alone or when activated by an SV40 early enhancer. One LTR, H6, displayed strong promoter activity in human (NTera2D1, 293, Hep2), monkey (COS-1), and mouse (3T3) cells. In fact, the activity of this LTR was similar to that of the SV40 early promoter/enhancer in 293, COS-1, and 3T3 cells. RNA mapping studies have localized the transcription start site to the expected location in the H6 LTR. RTVL-H LTRs were also shown to contain sequences which could increase transcription from the human beta-globin promoter and be influenced by SV40 enhancer sequences. As the human genome contains several hundred related RTVL-H sequences and a similar number of solitary LTRs, these findings raise the possibility that RTVL-H LTRs could have diverse effects on the expression of adjacent cellular genes. Images PMID:1690875

Feuchter, A; Mager, D

1990-01-01

109

RAB23 mutation in a large family from Comoros Islands with Carpenter syndrome.  

PubMed

We report here on a RAB23 mutation (c.86dupA) present in the homozygote state in four relatives of Comorian origin with Carpenter syndrome. All children presented with acrocephaly and polysyndactyly. However, intrafamilial variability was observed with variable severity of craniosynostosis ranging from cloverleaf skull to predominant involvement of the metopic ridge. All children also presented with a combination of brachydactyly with agenesis of the middle phalanges, syndactyly, broad thumbs, and postaxial polydactyly (2/4) in the hands, and preaxial polydactyly (3) and syndactyly (4) in the toes. Mental development was normal in all four children but the eldest one presented with impaired motor development as a result of orthopedic complications. Brain imaging showed hydrocephalus in 2/4 and additional features included genu valgum (2/4), abnormal genitalia (3/4), corneal anomaly (2/4), umbilical hernia (1/4), severe cyphoscoliosis (1), patent ductus arteriosus (1/4), and accessory spleen (1). In contrast to previous reports, growth was below average except for one patient and the eldest one became moderately overweight with time. We conclude from the report of this large unique family with four affected children that Carpenter syndrome is a genetically homogenous but a clinically variable condition. PMID:20358613

Alessandri, Jean-Luc; Dagoneau, Nathalie; Laville, Jean-Marc; Baruteau, Julien; Hébert, Jean-Christophe; Cormier-Daire, Valérie

2010-04-01

110

Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality.  

PubMed

The phosphatidylinositol glycan class A (PIGA) protein is a member of the glycosylphosphatidylinositol anchor pathway. Germline mutations in PIGA located at Xp22.2 are thought to be lethal in males. However, a nonsense mutation in the last coding exon was recently described in two brothers with multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) who survived through birth likely because of the hypomorphic nature of the truncated protein, but died in their first weeks of life. Here, we report on a frameshift mutation early in the PIGA cDNA (c.76dupT; p.Y26Lfs*3) that cosegregates with the disease in a large family diagnosed with a severe syndromic form of X-linked intellectual disability. Unexpectedly, CD59 surface expression suggested the production of a shorter PIGA protein with residual functionality. We provide evidence that the second methionine at position 37 may be used for the translation of a 36 amino acids shorter PIGA. Complementation assays confirmed that this shorter PIGA cDNA was able to partially rescue the surface expression of CD59 in a PIGA-null cell line. Taken together, our data strongly suggest that the early frameshift mutation in PIGA produces a truncated hypomorph, which is sufficient to rescue the lethality in males but not the MCAHS2-like phenotype. PMID:24357517

Belet, Stefanie; Fieremans, Nathalie; Yuan, Xuan; Van Esch, Hilde; Verbeeck, Jelle; Ye, Zhaohui; Cheng, Linzhao; Brodsky, Brett R; Hu, Hao; Kalscheuer, Vera M; Brodsky, Robert A; Froyen, Guy

2014-03-01

111

Familial gigantiform cementoma: distinctive clinical features of a large Chinese pedigree.  

PubMed

Familial gigantiform cementoma is a rare benign fibrocemento-osseous lesion of the jaws that can cause severe facial deformity. It has an autosomal dominant mode of inheritance, but varies in its phenotype. It is more common in white, African, and East-Asian patients. Here we report what is to our knowledge the first distinctive Chinese family with familial gigantiform cementoma involving 4 generations and 13 patients, and which suggests that the tumour presents with 3 distinctive growth phrases. PMID:25284619

Wang, H W; Yu, M; Qin, X J; Zhang, C P

2015-01-01

112

Family Activity Guide Family Activity Guide prepared by National Geographic and Destination Cinema, Inc., for the large-format  

E-print Network

.nationalgeographic.com/lewisandclark The Lewis and Clark Expedition was long and difficult. The group had to overcome many obstacles. They braved, Inc., for the large-format film Lewis & Clark: Great Journey West; and funded in part by the National Lewis to lead an important expedition. His assignment: Find an all-water route to the Pacific Ocean

Mathis, Wayne N.

113

Atrial fibrillation anticoagulation care in a large urban family medicine practice  

PubMed Central

Abstract Objective To determine the proportion of patients with atrial fibrillation (AF) in primary care achieving guideline-concordant stroke prevention treatment based on both the previous (2010) and the updated (2012) Canadian guideline recommendations. Design Retrospective chart review. Participants Primary care patients (N = 204) with AF. The mean age was 71.3 years and 53.4% were women. Setting Large urban community family practice in Toronto, Ont. Main outcome measures Patient demographic characteristics such as sex and age; a list of current cardiac medications including anticoagulants and antiplatelets; the total number of medications; relevant current and past medical history including presence of diabetes, stroke or transient ischemic attack, hypertension, and vascular disease; number of visits to the family physician and cardiologist in the past year and past 5 years, and how many of these were for AF; the number of visits to the emergency department or hospitalizations for AF, congestive heart failure, or stroke; if patients were taking warfarin, how often their international normalized ratios were recorded, and how many times they were in the reference range; CHADS2 (congestive heart failure, hypertension, age ? 75, diabetes mellitus, and stroke or transient ischemic attack) score, if recorded; and reason for not taking oral anticoagulants when they should have been, if recorded. Results Among those who had CHADS2 scores of 0, 64 patients (97.0%) were receiving appropriate stroke prevention in AF (SPAF) treatment according to the 2010 guidelines. When the 2012 guidelines were applied, 39 patients (59.1%) were receiving appropriate SPAF treatment (P < .001). For those with CHADS2 scores of 1, 88.4% of patients had appropriate SPAF treatment according to the 2010 guidelines, but only 55.1% were adequately treated according to the 2012 guidelines (P < .001). Of the patients at the highest risk (CHADS2 score > 1), 68.1% were adequately treated with anticoagulation and an additional 8.7% (6 of 69) had documented reasons why they were not taking anticoagulants. Conclusion When assessed using the 2012 Canadian Cardiovascular Society AF guidelines, the proportion of patients receiving appropriate SPAF therapy in this primary care setting decreased substantially. All patients with CHADS2 scores of 0 or 1 should be reassessed to ensure that they are receiving optimal stroke prevention treatment. PMID:24627401

Valentinis, Alissia; Ivers, Noah; Bhatia, Sacha; Meshkat, Nazanin; Leblanc, Kori; Ha, Andrew; Morra, Dante

2014-01-01

114

2q37 as a susceptibility locus for idiopathic basal ganglia calcification (IBGC) in a large South Tyrolean family.  

PubMed

Familial idiopathic basal ganglia calcification (FIBGC) is an inherited neurodegenerative disorder characterized by the accumulation of calcium deposits in different brain regions, particularly in the basal ganglia. FIBGC usually follows an autosomal dominant pattern of inheritance. Despite the mapping to chromosome 14q of a susceptibility locus for IBGC (IBCG1) in one family, this locus has been excluded in several others, demonstrating genetic heterogeneity in this disorder. The etiology of this disorder thus remains largely unknown. Using a large extended multigenerational Italian family from South Tyrol with 17 affected in a total of 56 members, we performed a genome-wide linkage analysis in which we were able to exclude linkage to the IBCG1 locus on chromosome 14q and obtain evidence of a novel locus on chromosome 2q37. Electronic supplementary material. The online version of this article (doi:10.1007/s12031-009-9287-3) contains supplementary material, which is available to authorized users. PMID:19757205

Volpato, Claudia Béu; De Grandi, Alessandro; Buffone, Ebba; Facheris, Maurizio; Gebert, Uwe; Schifferle, Günther; Schönhuber, Rudolf; Hicks, Andrew; Pramstaller, Peter P

2009-11-01

115

Between Acculturation and Ambivalence: Knowledge of Genetics and Attitudes towards Genetic Testing in a Consanguineous Bedouin Community  

Microsoft Academic Search

The Bedouins of the Negev (Southern part of Israel) are a community at increased risk for genetic diseases and congenital anomalies as a result of frequent consanguinity (particularly patrilateral parallel-cousin marriage) and underutilization of prenatal genetic tests due to a Muslim ban on abortion. Objective: To assess the knowledge and attitudes of Bedouin schoolchildren and their teachers towards a community-based,

Aviad E. Raz; Marcela Atar; Maya Rodnay; Ilana Shoham-Vardi; Rivka Carmi

2003-01-01

116

A novel homozygous 10 nucleotide deletion in BBS10 causes Bardet-Biedl syndrome in a Pakistani family.  

PubMed

Bardet-Biedl Syndrome is a multisystem autosomal recessive disorder characterized by central obesity, polydactyly, hypogonadism, learning difficulties, rod-cone dystrophy and renal dysplasia. Bardet-Biedl Syndrome has a prevalence rate ranging from 1 in 100,000 to 1 in 160,000 births although there are communities where Bardet-Biedl Syndrome is found at a higher frequency due to consanguinity. We report here a Pakistani consanguineous family with two affected sons with typical clinical features of Bardet-Biedl Syndrome, in addition to abnormal liver functioning and bilateral basal ganglia calcification, the latter feature being typical of Fahr's disease. Homozygous regions obtained from SNP array depicted three known genes BBS10, BBS14 and BBS2. Bidirectional sequencing of all coding exons by traditional sequencing of all these three genes showed a homozygous deletion of 10 nucleotides (c.1958_1967del), in BBS10 in both affected brothers. The segregation analysis revealed that the parents, paternal grandfather, maternal grandmother and an unaffected sister were heterozygous for the deletion. Such a large deletion in BBS10 has not been reported previously in any population and is likely to be contributing to the phenotype of Bardet-Biedl Syndrome in this family. PMID:23403234

Agha, Zehra; Iqbal, Zafar; Azam, Maleeha; Hoefsloot, Lies H; van Bokhoven, Hans; Qamar, Raheel

2013-04-25

117

Family dinner and disordered eating behaviors in a large cohort of adolescents  

PubMed Central

We aimed to examine longitudinal associations between family dinner and disordered eating behaviors among adolescents. We studied 7535 females and 5913 males, 9 to 14 years of age in 1996. We performed multivariable logistic regression to assess the associations of previous year family dinner with 1-year incidence of each of 3 outcomes: purging, binge eating, and frequent dieting. Compared to those who ate family dinner “never or some days,” female adolescents who ate family dinner at least most days were less likely to initiate purging, binge eating, and frequent dieting. Estimates of association among males were similar in direction and magnitude, although lower frequency of the outcomes resulted in less precise estimates and fewer statistically significant results. PMID:20390605

Haines, Jess; Gillman, Matthew W.; Rifas-Shiman, Sheryl; Field, Alison E.; Austin, S. Bryn

2009-01-01

118

ORIGINAL ARTICLE Familial steroid-sensitive nephrotic syndrome  

E-print Network

ORIGINAL ARTICLE Familial steroid-sensitive nephrotic syndrome in Southern Israel: clinical January 2007 # IPNA 2007 Abstract Reports on genetically informative steroid-re- sponsive (sensitive with a high rate of consanguinity. The clinical presentation and steroid response of its 11 affected

Friedman, Nir

119

Whole-proteome phylogeny of large dsDNA virus families by an alignment-free method  

PubMed Central

The vast sequence divergence among different virus groups has presented a great challenge to alignment-based sequence comparison among different virus families. Using an alignment-free comparison method, we construct the whole-proteome phylogeny for a population of viruses from 11 viral families comprising 142 large dsDNA eukaryote viruses. The method is based on the feature frequency profiles (FFP), where the length of the feature (l-mer) is selected to be optimal for phylogenomic inference. We observe that (i) the FFP phylogeny segregates the population into clades, the membership of each has remarkable agreement with current classification by the International Committee on the Taxonomy of Viruses, with one exception that the mimivirus joins the phycodnavirus family; (ii) the FFP tree detects potential evolutionary relationships among some viral families; (iii) the relative position of the 3 herpesvirus subfamilies in the FFP tree differs from gene alignment-based analysis; (iv) the FFP tree suggests the taxonomic positions of certain “unclassified” viruses; and (v) the FFP method identifies candidates for horizontal gene transfer between virus families. PMID:19553209

Wu, Guohong Albert; Jun, Se-Ran; Sims, Gregory E.; Kim, Sung-Hou

2009-01-01

120

A Novel PRPF31 Mutation in a Large Chinese Family with Autosomal Dominant Retinitis Pigmentosa and Macular Degeneration  

PubMed Central

Purpose This study was intended to identify the disease causing genes in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration. Methods A genome scan analysis was conducted in this family for disease gene preliminary mapping. Snapshot analysis of selected SNPs for two-point LOD score analysis for candidate gene filter. Candidate gene PRPF31 whole exons' sequencing was executed to identify mutations. Results A novel nonsense mutation caused by an insertion was found in PRPF31 gene. All the 19 RP patients in 1085 family are carrying this heterozygous nonsense mutation. The nonsense mutation is in PRPF31 gene exon9 at chr19:54629961-54629961, inserting nucleotide “A” that generates the coding protein frame shift from p.307 and early termination at p.322 in the snoRNA binding domain (NOP domain). Conclusion This report is the first to associate PRPF31 gene's nonsense mutation and adRP and JMD. Our findings revealed that PRPF31 can lead to different clinical phenotypes in the same family, resulting either in adRP or syndrome of adRP and JMD. We believe our identification of the novel “A” insertion mutation in exon9 at chr19:54629961-54629961 in PRPF31 can provide further genetic evidence for clinical test for adRP and JMD. PMID:24244300

Zheng, Hong; Liu, Xiaoqi; Yang, Jiyun; Shi, Yi; Lin, Ying; Gong, Bo; Zhu, Xianjun; Ma, Shi; Qiao, Lifeng; Lin, He; Cheng, Jing; Yang, Zhenglin

2013-01-01

121

Compound heterozygous PLEC mutations in a patient of consanguineous parentage with epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia.  

PubMed

Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD; OMIM 226670) is an autosomal recessive form of EBS, characterized by skin blistering at birth and delayed onset of muscle dystrophy. Mutations in PLEC, the gene encoding plectin, have been identified to be causal for EBS-MD. We report a case of EBS-MD with diffuse alopecia. Genetic study revealed the patient carrying compound heterozygous mutations in PLEC despite the consanguineous parentage. PMID:25209331

Yin, Jinghua; Ren, Yali; Lin, Zhimiao; Wang, Huijun; Zhou, Yun; Yang, Yong

2015-02-01

122

bZIPs and WRKYs: two large transcription factor families executing two different functional strategies  

PubMed Central

bZIPs and WRKYs are two important plant transcription factor (TF) families regulating diverse developmental and stress-related processes. Since a partial overlap in these biological processes is obvious, it can be speculated that they fulfill non-redundant functions in a complex regulatory network. Here, we focus on the regulatory mechanisms that are so far described for bZIPs and WRKYs. bZIP factors need to heterodimerize for DNA-binding and regulation of transcription, and based on a bioinformatics approach, bZIPs can build up more than the double of protein interactions than WRKYs. In contrast, an enrichment of the WRKY DNA-binding motifs can be found in WRKY promoters, a phenomenon which is not observed for the bZIP family. Thus, the two TF families follow two different functional strategies in which WRKYs regulate each other’s transcription in a transcriptional network whereas bZIP action relies on intensive heterodimerization. PMID:24817872

Llorca, Carles M.; Potschin, Maren; Zentgraf, Ulrike

2014-01-01

123

Evolution of a Large, Conserved, and Syntenic Gene Family in Insects  

PubMed Central

The Osiris gene family, first described in Drosophila melanogaster, is clustered in the genomes of all Drosophila species sequenced to date. In D. melanogaster, it explains the enigmatic phenomenon of the triplo-lethal and haploinsufficient locus Tpl. The synteny of Osiris genes in flies is well conserved, and it is one of the largest syntenic blocks in the Drosophila group. By examining the genome sequences of other insects in a wide range of taxonomic orders, we show here that the gene family is well-conserved and syntenic not only in the diptera but across the holometabolous and hemimetabolous insects. Osiris gene homologs have also been found in the expressed sequence tag sequences of various other insects but are absent from all groups that are not insects, including crustacea and arachnids. It is clear that the gene family evolved by gene duplication and neofunctionalization very soon after the divergence of the insects from other arthropods but before the divergence of the insects from one another and that the sequences and synteny have been maintained by selection ever since. PMID:22384409

Shah, Neethu; Dorer, Douglas R.; Moriyama, Etsuko N.; Christensen, Alan C.

2012-01-01

124

Tremulous cervical dystonia is likely to be familial: Clinical characteristics of a large cohort  

PubMed Central

Background Primary cervical dystonia is the most common form of adult-onset focal dystonia. Although most frequently sporadic, 15–20% of patients report a positive family history, suggesting a possible genetic cause. Head tremor is often present in patients with cervical dystonia and may be a prominent symptom. Objective To describe the clinical characteristics of patients with tremulous cervical dystonia. Methods Patients with primary cervical dystonia attending our botulinum toxin clinic were assessed with an interview and neurological examination and their notes reviewed. Patients were classified as having either tremulous or non-tremulous cervical dystonia, according to the presence or absence of head tremor on examination. Clinical and demographic data were compared between groups. Results From 273 patients included (190 females, 83 males), 125 (46%) were classified as tremulous and 148 (54%) as non-tremulous. Tremulous patients were more likely to have a segmental distribution (61% vs 25%), often involving the arms (48%), and had more frequently associated arm tremor (55% vs 10%). A positive family history of dystonia and/or tremor was more frequent in tremulous patients (50% vs 18%). Conclusions Patients with cervical dystonia with associated head tremor are more likely to have a segmental distribution (with frequent arm involvement), associated arm tremor and a positive family history, suggesting a genetic etiology in this subgroup of patients. PMID:23523105

Rubio-Agusti, I.; Pareés, I.; Kojovic, M.; Stamelou, M.; Saifee, T.A.; Charlesworth, G.; Sheerin, U.M.; Edwards, M.J.; Bhatia, K.P.

2014-01-01

125

Evolution of a large, conserved, and syntenic gene family in insects.  

PubMed

The Osiris gene family, first described in Drosophila melanogaster, is clustered in the genomes of all Drosophila species sequenced to date. In D. melanogaster, it explains the enigmatic phenomenon of the triplo-lethal and haploinsufficient locus Tpl. The synteny of Osiris genes in flies is well conserved, and it is one of the largest syntenic blocks in the Drosophila group. By examining the genome sequences of other insects in a wide range of taxonomic orders, we show here that the gene family is well-conserved and syntenic not only in the diptera but across the holometabolous and hemimetabolous insects. Osiris gene homologs have also been found in the expressed sequence tag sequences of various other insects but are absent from all groups that are not insects, including crustacea and arachnids. It is clear that the gene family evolved by gene duplication and neofunctionalization very soon after the divergence of the insects from other arthropods but before the divergence of the insects from one another and that the sequences and synteny have been maintained by selection ever since. PMID:22384409

Shah, Neethu; Dorer, Douglas R; Moriyama, Etsuko N; Christensen, Alan C

2012-02-01

126

Phenotype of chromosome 14-linked familial Alzheimer's disease in a large kindred.  

PubMed

We report the clinical and neuropathological features of chromosome 14-linked familial Alzheimer's disease (14qFAD) in affected members of the L family. Some clinical information on all 16 known affected individuals and detailed neuropathological findings in 6 family members were available for review. Common features of the phenotype of 14qFAD in the L family included onset of dementia before the age of 50, early progressive aphasia, early-appearing myoclonus and generalized seizures, paratonia, cortical atrophy, numerous and extensive senile plaques and neurofibrillary tangles, and prominent amyloid angiopathy. Descriptions of phenotypic features were available for six additional recently defined 14q-linked FAD kindreds: the findings in four of them (FAD4, FAD2, A, B) indicated a relatively consistently shared 14qFAD phenotype, conforming closely with the specific clinical and neuropathological characteristics noted in the L family. Comparisons also suggested several ostensible phenotypic variants in 14qFAD: (1) In two 14q-linked kindreds (SNW/FAD3, FAD1), affected individuals in some instances were noted to survive to age 70 or beyond and the mean age at onset (> 49 years) in these two kindreds was somewhat higher than in their five 14qFAD counterparts (< 48 years in each); (2) in the SNW/FAD3 kindred, seizures and myoclonus were absent in all 10 subjects examined; and (3) cerebellar amyloid plaques were variably present within and among several 14qFAD kindreds. Comparisons with phenotypic features recently detailed in three kindreds (TOR3, F19, ROM) with codon 717 amyloid precursor protein gene mutations (i.e., APP717 FAD) suggested several distinctions: Prominent progressive aphasia, myoclonus, seizures, and paratonia were all apparently less prevalent in APP717 FAD, with language function predominantly spared over the initial disease course. The extent of homogeneity and heterogeneity in the clinical and neuropathological phenotype of 14q-linked FAD and its possible meaningful distinctions from the phenotypes of APP717 FAD await further determination. PMID:8080245

Lampe, T H; Bird, T D; Nochlin, D; Nemens, E; Risse, S C; Sumi, S M; Koerker, R; Leaird, B; Wier, M; Raskind, M A

1994-09-01

127

Common Functions or Only Phylogenetically Related? The Large Family of PLAC8 Motif-Containing/PCR Genes  

PubMed Central

PLAC8 motif-containing proteins form a large family and members can be found in fungi, algae, higher plants and animals. They include the PCR proteins of plants. The name giving PLAC8 domain was originally found in a protein residing in the spongiotrophoblast layer of the placenta of mammals. A further motif found in a large number of these proteins including several PCR proteins is the CCXXXXCPC or CLXXXXCPC motif. Despite their wide distribution our knowledge about the function of these proteins is very limited. For most of them two membranespanning ?-helices are predicted, indicating that they are membrane associated or membrane intrinsic proteins. In plants PLAC8 motif-containing proteins have been described to be implicated in two very different functions. On one hand, it has been shown that they are involved in the determination of fruit size and cell number. On the other hand, two members of this family, AtPCR1 and AtPCR2 play an important role in transport of heavy metals such as cadmium or zinc. Transport experiments and approaches to model the 3_D structure of these proteins indicate that they could act as transporters for these divalent cations by forming homomultimers. In this minireview we discuss the present knowledge about this protein family and try to give an outlook on how to integrate the different proposed functions into a common picture about the role of PLAC8 motif-containing proteins. PMID:21347707

Song, Won-Yong; Hörtensteiner, Stefan; Tomioka, Rie; Lee, Youngsook; Martinoia, Enrico

2011-01-01

128

Power of family-based association designs to detect rare variants in large pedigrees using imputed genotypes.  

PubMed

Recently, the "Common Disease-Multiple Rare Variants" hypothesis has received much attention, especially with current availability of next-generation sequencing. Family-based designs are well suited for discovery of rare variants, with large and carefully selected pedigrees enriching for multiple copies of such variants. However, sequencing a large number of samples is still prohibitive. Here, we evaluate a cost-effective strategy (pseudosequencing) to detect association with rare variants in large pedigrees. This strategy consists of sequencing a small subset of subjects, genotyping the remaining sampled subjects on a set of sparse markers, and imputing the untyped markers in the remaining subjects conditional on the sequenced subjects and pedigree information. We used a recent pedigree imputation method (GIGI), which is able to efficiently handle large pedigrees and accurately impute rare variants. We used burden and kernel association tests, famWS and famSKAT, which both account for family relationships and heterogeneity of allelic effect for famSKAT only. We simulated pedigree sequence data and compared the power of association tests for pseudosequence data, a subset of sequence data used for imputation, and all subjects sequenced. We also compared, within the pseudosequence data, the power of association test using best-guess genotypes and allelic dosages. Our results show that the pseudosequencing strategy considerably improves the power to detect association with rare variants. They also show that the use of allelic dosages results in much higher power than use of best-guess genotypes in these family-based data. Moreover, famSKAT shows greater power than famWS in most of scenarios we considered. PMID:24243664

Saad, Mohamad; Wijsman, Ellen M

2014-01-01

129

Study of large inbred Friedreich ataxia families reveals a recombination between D9S15 and the disease locus  

PubMed Central

Friedreich ataxia is a neurodegenerative disorder with autosomal recessive inheritance. Precise linkage mapping of the Friedreich ataxia locus (FRDA) in 9q13-q21 should lead to the isolation of the defective gene by positional cloning. The two closest DNA markers, D9S5 and D9S15, show very tight linkage to FRDA, making difficult the ordering of the three loci. We present a linkage study of three large Friedreich ataxia families of Tunisian origin, with several multiallelic markers around D9S5 and D9S15. Haplotype data were used to investigate genetic homogeneity of the disease in these geographically related families. A meiotic recombination was found in a nonaffected individual, which excludes a 150-kb segment, including D9S15, as a possible location for the Friedreich ataxia gene and which should orient the search in the D9S5 region. PMID:1463017

Belal, Samir; Panayides, Kyproula; Sirugo, Giorgio; Hamida, Christiane Ben; Ioannou, Panos; Hentati, Fayçal; Beckmann, Jacques; Koenig, Michel; Mandel, Jean-Louis; Hamida, Mongi Ben; Middleton, Lefkos T.

1992-01-01

130

Bracoviruses Contain a Large Multigene Family Coding for Protein Tyrosine Phosphatases  

PubMed Central

The relationship between parasitic wasps and bracoviruses constitutes one of the few known mutualisms between viruses and eukaryotes. The virions produced in the wasp ovaries are injected into host lepidopteran larvae, where virus genes are expressed, allowing successful development of the parasite by inducing host immune suppression and developmental arrest. Bracovirus-bearing wasps have a common phylogenetic origin, and contemporary bracoviruses are hypothesized to have been inherited by chromosomal transmission from a virus that originally integrated into the genome of the common ancestor wasp living 73.7 ± 10 million years ago. However, so far no conserved genes have been described among different braconid wasp subfamilies. Here we show that a gene family is present in bracoviruses of different braconid wasp subfamilies (Cotesia congregata, Microgastrinae, and Toxoneuron nigriceps, Cardiochilinae) which likely corresponds to an ancient component of the bracovirus genome that might have been present in the ancestral virus. The genes encode proteins belonging to the protein tyrosine phosphatase family, known to play a key role in the control of signal transduction pathways. Bracovirus protein tyrosine phosphatase genes were shown to be expressed in different tissues of parasitized hosts, and two protein tyrosine phosphatases were produced with recombinant baculoviruses and tested for their biochemical activity. One protein tyrosine phosphatase is a functional phosphatase. These results strengthen the hypothesis that protein tyrosine phosphatases are involved in virally induced alterations of host physiology during parasitism. PMID:15542661

Provost, Bertille; Varricchio, Paola; Arana, Eloisa; Espagne, Eric; Falabella, Patrizia; Huguet, Elisabeth; La Scaleia, Raffaella; Cattolico, Laurence; Poirié, Marylène; Malva, Carla; Olszewski, Julie A.; Pennacchio, Francesco; Drezen, Jean-Michel

2004-01-01

131

Bracoviruses contain a large multigene family coding for protein tyrosine phosphatases.  

PubMed

The relationship between parasitic wasps and bracoviruses constitutes one of the few known mutualisms between viruses and eukaryotes. The virions produced in the wasp ovaries are injected into host lepidopteran larvae, where virus genes are expressed, allowing successful development of the parasite by inducing host immune suppression and developmental arrest. Bracovirus-bearing wasps have a common phylogenetic origin, and contemporary bracoviruses are hypothesized to have been inherited by chromosomal transmission from a virus that originally integrated into the genome of the common ancestor wasp living 73.7 +/- 10 million years ago. However, so far no conserved genes have been described among different braconid wasp subfamilies. Here we show that a gene family is present in bracoviruses of different braconid wasp subfamilies (Cotesia congregata, Microgastrinae, and Toxoneuron nigriceps, Cardiochilinae) which likely corresponds to an ancient component of the bracovirus genome that might have been present in the ancestral virus. The genes encode proteins belonging to the protein tyrosine phosphatase family, known to play a key role in the control of signal transduction pathways. Bracovirus protein tyrosine phosphatase genes were shown to be expressed in different tissues of parasitized hosts, and two protein tyrosine phosphatases were produced with recombinant baculoviruses and tested for their biochemical activity. One protein tyrosine phosphatase is a functional phosphatase. These results strengthen the hypothesis that protein tyrosine phosphatases are involved in virally induced alterations of host physiology during parasitism. PMID:15542661

Provost, Bertille; Varricchio, Paola; Arana, Eloisa; Espagne, Eric; Falabella, Patrizia; Huguet, Elisabeth; La Scaleia, Raffaella; Cattolico, Laurence; Poirié, Marylène; Malva, Carla; Olszewski, Julie A; Pennacchio, Francesco; Drezen, Jean-Michel

2004-12-01

132

Large Deletion in KCNQ1 Identified in a Family with Jervell and Lange-Nielsen Syndrome  

PubMed Central

Long QT syndrome (LQTS) is a genetically heterogeneous disorder associated with sequence variations in more than 10 genes; in some cases, it is caused by large deletions or duplications among the main, known LQTS-associated genes. Here, we describe a 14-month-old Korean boy with congenital hearing loss and prolonged QT interval whose condition was clinically diagnosed as Jervell and Lange-Nielsen syndrome (JLNS), a recessive form of LQTS. Genetic analyses using sequence analysis and multiplex ligation-dependent probe amplification (MLPA) assay revealed a large deletion spanning exons 7-10 as well as a frameshift mutation (c.1893dup; p.Arg632Glnfs*20). To our knowledge, this is the first report of a large deletion in KCNQ1 identified in JLNS patients. This case indicates that a method such as MLPA, which can identify large deletions or duplications needs to be considered in addition to sequence analysis to diagnose JLNS. PMID:25187895

Sung, Ji Yeon; Bae, Eun Jung; Park, Seungman; Kim, So Yeon; Hyun, Ye Jin; Park, Sung Sup

2014-01-01

133

Age distribution of human gene families shows significant roles of both large- and small-scale duplications in vertebrate evolution.  

PubMed

The classical (two-round) hypothesis of vertebrate genome duplication proposes two successive whole-genome duplication(s) (polyploidizations) predating the origin of fishes, a view now being seriously challenged. As the debate largely concerns the relative merits of the 'big-bang mode' theory (large-scale duplication) and the 'continuous mode' theory (constant creation by small-scale duplications), we tested whether a significant proportion of paralogous genes in the contemporary human genome was indeed generated in the early stage of vertebrate evolution. After an extensive search of major databases, we dated 1,739 gene duplication events from the phylogenetic analysis of 749 vertebrate gene families. We found a pattern characterized by two waves (I, II) and an ancient component. Wave I represents a recent gene family expansion by tandem or segmental duplications, whereas wave II, a rapid paralogous gene increase in the early stage of vertebrate evolution, supports the idea of genome duplication(s) (the big-bang mode). Further analysis indicated that large- and small-scale gene duplications both make a significant contribution during the early stage of vertebrate evolution to build the current hierarchy of the human proteome. PMID:12032571

Gu, Xun; Wang, Yufeng; Gu, Jianying

2002-06-01

134

A family of derivative-free conjugate gradient methods for large-scale nonlinear systems of equations  

NASA Astrophysics Data System (ADS)

In this paper, we propose a family of derivative-free conjugate gradient methods for large-scale nonlinear systems of equations. They come from two modified conjugate gradient methods [W.Y. Cheng, A two term PRP based descent Method, Numer. Funct. Anal. Optim. 28 (2007) 1217-1230; L. Zhang, W.J. Zhou, D.H. Li, A descent modified Polak-Ribiére-Polyak conjugate gradient method and its global convergence, IMA J. Numer. Anal. 26 (2006) 629-640] recently proposed for unconstrained optimization problems. Under appropriate conditions, the global convergence of the proposed method is established. Preliminary numerical results show that the proposed method is promising.

Cheng, Wanyou; Xiao, Yunhai; Hu, Qing-Jie

2009-02-01

135

Exome Sequencing Identifies a Dominant TNNT3 Mutation in a Large Family with Distal Arthrogryposis  

PubMed Central

Distal arthrogryposis (DA) is a group of rare, clinically and genetically heterogeneous disorders primarily characterized by congenital contractures of the distal limb joints without a neuromuscular disease. Mutations in at least 8 different genes have been shown to cause DA. Here, we report a 4-generation Indian family with 18 affected members presenting variable features of camptodactyly, brachydactyly, syndactyly, decreased flexion palmar creases, ulnar deviation of the hands, sandal gaps and club feet. We undertook exome sequencing of 3 distantly related affected individuals. Bioinformatics filtering revealed a known pathogenic missense mutation c.188G>A (p.Arg63His) in TNNT3 in all 3 affected individuals that segregated with the phenotype. The affected individuals exhibit significant phenotypic variability. This study demonstrates the value of exome sequencing helping to define the causative variant in genetically heterogeneous disorders. PMID:25337069

Daly, Sarah B.; Shah, Hitesh; O'Sullivan, James; Anderson, Beverley; Bhaskar, Sanjeev; Williams, Simon; Al-Sheqaih, Nada; Mueed Bidchol, Abdul; Banka, Siddharth; Newman, William G.; Girisha, Katta M.

2014-01-01

136

Exome Sequencing of 75 Individuals from Multiply Affected Coeliac Families and Large Scale Resequencing Follow Up  

PubMed Central

Coeliac disease (CeD) is a highly heritable common autoimmune disease involving chronic small intestinal inflammation in response to dietary wheat. The human leukocyte antigen (HLA) region, and 40 newer regions identified by genome wide association studies (GWAS) and dense fine mapping, account for ?40% of the disease heritability. We hypothesized that in pedigrees with multiple individuals with CeD rare [minor allele frequency (MAF) <0.5%] mutations of larger effect size (odds ratios of ? 2–5) might exist. We sequenced the exomes of 75 coeliac individuals of European ancestry from 55 multiply affected families. We selected interesting variants and genes for further follow up using a combination of: an assessment of shared variants between related subjects, a model-free linkage test, and gene burden tests for multiple, potentially causal, variants. We next performed highly multiplexed amplicon resequencing of all RefSeq exons from 24 candidate genes selected on the basis of the exome sequencing data in 2,248 unrelated coeliac cases and 2,230 controls. 1,335 variants with a 99.9% genotyping call rate were observed in 4,478 samples, of which 939 were present in coding regions of 24 genes (Ti/Tv 2.99). 91.7% of coding variants were rare (MAF <0.5%) and 60% were novel. Gene burden tests performed on rare functional variants identified no significant associations (p<1×10?3) in the resequenced candidate genes. Our strategy of sequencing multiply affected families with deep follow up of candidate genes has not identified any new CeD risk mutations. PMID:25635822

Mistry, Vanisha; Bockett, Nicholas A.; Levine, Adam P.; Mirza, Muddassar M.; Hunt, Karen A.; Ciclitira, Paul J.; Hummerich, Holger; Neuhausen, Susan L.; Simpson, Michael A.; Plagnol, Vincent; van Heel, David A.

2015-01-01

137

Familial Mediterranean Fever Associated with MEFV Mutations in a Large Cohort of Cypriot Patients.  

PubMed

Familial Mediterranean fever (FMF) is caused by mutations in the MEFV gene and the spectrum of mutations among Greek-Cypriots with FMF-related symptoms was examined. Sequence analysis for exons 2, 3, 5, and 10 of the MEFV gene was performed in a cohort of 593 patients. A total of 70 patients carried mutations in the homozygote or compound heterozygote state, 128 were identified with one MEFV mutation and 395 had no mutations. Of the 268 identified alleles, p.Val726Ala (27.61%) was the most frequent followed by p.Met694Val (19.40%). The missense mutations p.Arg761His (3.73%) and p.Ala744Ser (2.24%) were identified as the rarest. An interesting finding is the high frequency (18.28%) of the complex p.Phe479Leu-p.Glu167Asp that was identified in 49 of the mutated alleles. The MEFV genotypes did not follow a binomial distribution and proved not to satisfy the HWE (P < 0.001). The high percentage (66.61%) of patients with unidentified mutations could be due to mutations in the rest of the coding or noncoding MEFV gene or due to mutations in other genes that are also causing Hereditary Recurrent Fevers. Results from this work indicate the high incidence of FMF in Cyprus and describe the spectrum of the mutations which occur in the country. PMID:25393764

Neocleous, Vassos; Costi, Constantina; Kyriakou, Christina; Kyriakides, Tassos C; Shammas, Christos; Skordis, Nicos; Toumba, Meropi; Kyriakou, Sophia; Koliou, Maria; Kousparou, Marianna; Onoufriou, Margarita; Hadjipanayis, Adamos; Iasonides, Michalis; Atamyan, Vick N; Pierides, Alkis; Christophidou-Anastasiadou, Violetta; Tanteles, George A; Phylactou, Leonidas A

2015-01-01

138

Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families.  

PubMed

In communities with high rates of consanguinity and consequently high prevalence of recessive phenotypes, homozygosity mapping with SNP arrays is an effective approach for gene discovery. In 20 Palestinian kindreds with prelingual nonsyndromic hearing loss, we generated homozygosity profiles reflecting linkage to the phenotype. Family sizes ranged from small nuclear families with two affected children, one unaffected sibling, and parents to multigenerational kindreds with 12 affected relatives. By including unaffected parents and siblings and screening 250 K SNP arrays, even small nuclear families yielded informative profiles. In 14 families, we identified the allele responsible for hearing loss by screening a single candidate gene in the longest homozygous region. Novel alleles included missense, nonsense, and splice site mutations of CDH23, MYO7A, MYO15A, OTOF, PJVK, Pendrin/SLC26A4, TECTA, TMHS, and TMPRSS3, and a large genomic deletion of Otoancorin (OTOA). All point mutations were rare in the Palestinian population (zero carriers in 288 unrelated controls); the carrier frequency of the OTOA genomic deletion was 1%. In six families, we identified five genomic regions likely to harbor novel genes for human hearing loss on chromosomes 1p13.3 (DFNB82), 9p23-p21.2/p13.3-q21.13 (DFNB83), 12q14.3-q21.2 (DFNB84; two families), 14q23.1-q31.1, and 17p12-q11.2 (DFNB85). PMID:19888295

Shahin, Hashem; Walsh, Tom; Rayyan, Amal Abu; Lee, Ming K; Higgins, Jake; Dickel, Diane; Lewis, Kristen; Thompson, James; Baker, Carl; Nord, Alex S; Stray, Sunday; Gurwitz, David; Avraham, Karen B; King, Mary-Claire; Kanaan, Moien

2010-04-01

139

A mutation in CTSK gene in an autosomal recessive pycnodysostosis family of Pakistani origin  

Microsoft Academic Search

BACKGROUND: Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acro-osteolysis, frequent fractures and skull deformities. Mutations in the gene encoding cathepsin K (CTSK), a lysosomal cysteine protease, have been found to be responsible for this disease. OBJECTIVES: To identify pathogenic mutation in a consanguineous Pakistani family with 3 affected individuals demonstrating autosomal recessive pycnodysostosis. METHODS:

Muhammad Naeem; Sabeen Sheikh; Wasim Ahmad

2009-01-01

140

Living in a Large Family Does Something For You: Influence of Family on the Achievement of African and Caribbean Women in Science.  

ERIC Educational Resources Information Center

Examines the influence of the family on women's achievement in scientific careers in the sub-Saharan African and Caribbean regions. Concludes that when compared with their North American and European counterparts, there are significant differences in the family experiences of African and Caribbean women scientists. (Author/SAH)

Beoku-Betts, Josephine A.

2000-01-01

141

A Large Family of Antivirulence Regulators Modulates the Effects of Transcriptional Activators in Gram-negative Pathogenic Bacteria  

PubMed Central

We have reported that transcription of a hypothetical small open reading frame (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44–100% similarity to at least fifty previously undescribed small (<10 kDa) hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator) for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this family. PMID:24875828

Santiago, Araceli E.; Ruiz-Perez, Fernando; Jo, Noah Y.; Vijayakumar, Vidhya; Gong, Mei Q.; Nataro, James P.

2014-01-01

142

Targeted high-throughput sequencing identifies pathogenic mutations in KCNQ4 in two large Chinese families with autosomal dominant hearing loss.  

PubMed

Autosomal dominant non-syndromic hearing loss (ADNSHL) is highly heterogeneous, among them, KCNQ4 is one of the most frequent disease-causing genes. More than twenty KCNQ4 mutations have been reported, but none of them were detected in Chinese mainland families. In this study, we identified a novel KCNQ4 mutation in a five generation Chinese family with 84 members and a known KCNQ4 mutation in a six generation Chinese family with 66 members. Mutation screening of 30 genes for ADNSHL was performed in the probands from thirty large Chinese families with ADNSHL by targeted region capture and high-throughput sequencing. The candidate variants and the co-segregation of the phenotype were verified by polymerase chain reaction (PCR) amplification and Sanger sequencing in all ascertained family members. Then we identified a novel KCNQ4 mutation p.W275R in exon 5 and a known KCNQ4 mutation p.G285S in exon 6 in two large Chinese ADNSHL families segregating with post-lingual high frequency-involved and progressive sensorineural hearing loss. This is the first report of KCNQ4 mutation in Chinese mainland families. KCNQ4, a member of voltage-gated potassium channel family, is likely to be a common gene in Chinese patients with ADNSHL. The results also support that the combination of targeted enrichment and high-throughput sequencing is a valuable molecular diagnostic tool for autosomal dominant hereditary deafness. PMID:25116015

Wang, Hongyang; Zhao, Yali; Yi, Yuting; Gao, Yun; Liu, Qiong; Wang, Dayong; Li, Qian; Lan, Lan; Li, Na; Guan, Jing; Yin, Zifang; Han, Bing; Zhao, Feifan; Zong, Liang; Xiong, Wenping; Yu, Lan; Song, Lijie; Yi, Xin; Yang, Ling; Petit, Christine; Wang, Qiuju

2014-01-01

143

Targeted High-Throughput Sequencing Identifies Pathogenic Mutations in KCNQ4 in Two Large Chinese Families with Autosomal Dominant Hearing Loss  

PubMed Central

Autosomal dominant non-syndromic hearing loss (ADNSHL) is highly heterogeneous, among them, KCNQ4 is one of the most frequent disease-causing genes. More than twenty KCNQ4 mutations have been reported, but none of them were detected in Chinese mainland families. In this study, we identified a novel KCNQ4 mutation in a five generation Chinese family with 84 members and a known KCNQ4 mutation in a six generation Chinese family with 66 members. Mutation screening of 30 genes for ADNSHL was performed in the probands from thirty large Chinese families with ADNSHL by targeted region capture and high-throughput sequencing. The candidate variants and the co-segregation of the phenotype were verified by polymerase chain reaction (PCR) amplification and Sanger sequencing in all ascertained family members. Then we identified a novel KCNQ4 mutation p.W275R in exon 5 and a known KCNQ4 mutation p.G285S in exon 6 in two large Chinese ADNSHL families segregating with post-lingual high frequency-involved and progressive sensorineural hearing loss. This is the first report of KCNQ4 mutation in Chinese mainland families. KCNQ4, a member of voltage-gated potassium channel family, is likely to be a common gene in Chinese patients with ADNSHL. The results also support that the combination of targeted enrichment and high-throughput sequencing is a valuable molecular diagnostic tool for autosomal dominant hereditary deafness. PMID:25116015

Gao, Yun; Liu, Qiong; Wang, Dayong; Li, Qian; Lan, Lan; Li, Na; Guan, Jing; Yin, Zifang; Han, Bing; Zhao, Feifan; Zong, Liang; Xiong, Wenping; Yu, Lan; Song, Lijie; Yi, Xin; Yang, Ling; Petit, Christine; Wang, Qiuju

2014-01-01

144

The Crystal Structure of Bacteriophage HK97 gp6: Defining a Large Family of Head?Tail Connector Proteins  

SciTech Connect

The final step in the morphogenesis of long-tailed double-stranded DNA bacteriophages is the joining of the DNA-filled head to the tail. The connector is a specialized structure of the head that serves as the interface for tail attachment and the point of egress for DNA from the head during infection. Here, we report the determination of a 2.1 {angstrom} crystal structure of gp6 of bacteriophage HK97. Through structural comparisons, functional studies, and bioinformatic analysis, gp6 has been determined to be a component of the connector of phage HK97 that is evolutionarily related to gp15, a well-characterized connector component of bacteriophage SPP1. Whereas the structure of gp15 was solved in a monomeric form, gp6 crystallized as an oligomeric ring with the dimensions expected for a connector protein. Although this ring is composed of 13 subunits, which does not match the symmetry of the connector within the phage, sequence conservation and modeling of this structure into the cryo-electron microscopy density of the SPP1 connector indicate that this oligomeric structure represents the arrangement of gp6 subunits within the mature phage particle. Through sequence searches and genomic position analysis, we determined that gp6 is a member of a large family of connector proteins that are present in long-tailed phages. We have also identified gp7 of HK97 as a homologue of gp16 of phage SPP1, which is the second component of the connector of this phage. These proteins are members of another large protein family involved in connector assembly.

Cardarelli, Lia; Lam, Robert; Tuite, Ashleigh; Baker, Lindsay A.; Sadowski, Paul D.; Radford, Devon R.; Rubinstein, John L.; Battaile, Kevin P.; Chirgadze, Nickolay; Maxwell, Karen L.; Davidson, Alan R. (UHN); (Toronto); (Hauptman)

2010-08-17

145

Familial chondrocalcinosis in the Chiloe Islands, Chile.  

PubMed

Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group. PMID:168817

Reginato, A J; Hollander, J L; Martinez, V; Valenzuela, F; Schiapachasse, V; Covarrubias, E; Jacobelli, S; Arinoviche, R; Silcox, D; Ruiz, F

1975-06-01

146

Familial chondrocalcinosis in the Chiloe Islands, Chile.  

PubMed Central

Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group. PMID:168817

Reginato, A J; Hollander, J L; Martinez, V; Valenzuela, F; Schiapachasse, V; Covarrubias, E; Jacobelli, S; Arinoviche, R; Silcox, D; Ruiz, F

1975-01-01

147

A canonical splice site mutation in GIPC3 causes sensorineural hearing loss in a large Pakistani family.  

PubMed

With homozygosity mapping we have identified two large homozygous regions on chromosome 3q13.11-q13.31 and chromosome 19p13.3-q31.32 in a large Pakistani family suffering from autosomal recessive nonsyndromic hearing impairment (arNSHI). The region on chromosome 19 overlaps with the previously described deafness loci DFNB15, DFNB72 and DFNB95. Mutations in GIPC3 have been shown to underlie the nonsyndromic hearing impairment linked to these loci. Sequence analysis of all exons and exon-intron boundaries of GIPC3 revealed a homozygous canonical splice site mutation, c.226-1G>T, in GIPC3. This is the first mutation described in GIPC3 that affects splicing. The c.226-1G>T mutation is located in the acceptor splice site of intron 1 and is predicted to affect the normal splicing of exon 2. With a minigene assay it was shown to result in the use of an alternative acceptor site in exon 2, resulting in a frameshift and a premature stop codon. This study expands the mutational spectrum of GIPC3 in arNSHI. PMID:25296581

Siddiqi, Saima; Ismail, Muhammad; Oostrik, Jaap; Munawar, Saba; Mansoor, Atika; Kremer, Hannie; Qamar, Raheel; Schraders, Margit

2014-12-01

148

Accuracy of genomic selection models in a large population of open-pollinated families in white spruce.  

PubMed

Genomic selection (GS) is of interest in breeding because of its potential for predicting the genetic value of individuals and increasing genetic gains per unit of time. To date, very few studies have reported empirical results of GS potential in the context of large population sizes and long breeding cycles such as for boreal trees. In this study, we assessed the effectiveness of marker-aided selection in an undomesticated white spruce (Picea glauca (Moench) Voss) population of large effective size using a GS approach. A discovery population of 1694 trees representative of 214 open-pollinated families from 43 natural populations was phenotyped for 12 wood and growth traits and genotyped for 6385 single-nucleotide polymorphisms (SNPs) mined in 2660 gene sequences. GS models were built to predict estimated breeding values using all the available SNPs or SNP subsets of the largest absolute effects, and they were validated using various cross-validation schemes. The accuracy of genomic estimated breeding values (GEBVs) varied from 0.327 to 0.435 when the training and the validation data sets shared half-sibs that were on average 90% of the accuracies achieved through traditionally estimated breeding values. The trend was also the same for validation across sites. As expected, the accuracy of GEBVs obtained after cross-validation with individuals of unknown relatedness was lower with about half of the accuracy achieved when half-sibs were present. We showed that with the marker densities used in the current study, predictions with low to moderate accuracy could be obtained within a large undomesticated population of related individuals, potentially resulting in larger gains per unit of time with GS than with the traditional approach. PMID:24781808

Beaulieu, J; Doerksen, T; Clément, S; MacKay, J; Bousquet, J

2014-10-01

149

Living in a Large Family does Something for You: Influence of Family on the Achievement of African and Caribbean Women in Science  

Microsoft Academic Search

This article examines the influence of the family on women's achievement in scientific careers in the sub-Saharan African and Caribbean regions. It is based on semistructured interviews with 20 doctoral-level African and Caribbean women scientists working in research and academic institutions in these societies. Given the diversity of structural conditions, and economic, geopolitical, and sociocultural experiences, it is argued that

Josephine A. Beoku-Betts

2000-01-01

150

Longitudinal and cross-sectional phenotype analysis in a new, large Dutch DFNA2/KCNQ4 family.  

PubMed

We analyzed hearing thresholds, speech recognition scores, and vestibular responses in 32 affected persons in a large family with DFNA2/KCNQ4-related hearing impairment caused by a W276S missense mutation. Linear regression analysis of individual longitudinal data revealed significant threshold progression (1 dB/y) and offset (at age zero). The mean offset thresholds were 5, 21, 40, 39, 31, and 51 dB hearing level (HL) at 0.25, 0.5, 1, 2, 4, and 8 kHz, respectively. Cross-sectional analysis of last-visit thresholds against age produced less-steep slopes and higher offset thresholds. Nonlinear regression analysis of last-visit phoneme recognition scores against age in 25 cases showed that speech recognition did not deteriorate before the third decade. A hyperactive vestibuloocular reflex was found in 3 of 11 cases: 2 persons were especially susceptible to motion sickness. Persons with this KCNQ4 mutation showed congenital, progressive high-frequency impairment without substantial loss of speech recognition during the first decades of life. PMID:11915881

De Leenheer, Els M R; Huygen, Patrick L M; Coucke, Paul J; Admiraal, Ronald J C; van Camp, G; Cremers, Cor W

2002-03-01

151

The second example of anti-K22 and a family genetically informative for K and K22.  

PubMed

The second example of anti-K22 was found, like the first, in an Iranian Jew living in Israel. The consanguineous parents of the propositus were both K+k+, and investigation of the family suggested that K22 is controlled by the Kell locus; K travelling with K22 and k with K-22. PMID:4036083

Manny, N; Levene, C; Harel, N; Schneiderman, S; Simon, A; Daniels, G L

1985-01-01

152

Mapping of a possible X-linked form of familial developmental dysphasia (FDD) in a single large pedigree  

SciTech Connect

Children diagnosed with developmental dysphasia develop speech very late without exhibiting sensory or motor dysfunction, and when they do begin to speak their grammar is abnormal. A large three-generation British pedigree was recently identified in which 16 out of 30 members were diagnosed as dysphasic. Assuming a dominant mode of inheritance with homogeneous phenotypic expression and complete penetrance among affected members, we showed by simulation analysis that this pedigree has the power to detect linkage to marker loci with an average maximum LOD score of 3.67 at {theta}=0.1. Given the absence of male-to-male transmission and a ratio of female to male affecteds (10/6) in this pedigree within the expected range for an X-linked dominant mode of inheritance, we decided to begin a genome-wide linkage analysis with microsatellite markers on the human X chromosome. Fifteen individuals (10 affected) from three generations were genotyped with 35 polymorphic STS`s (Research Genetics) which were approximately uniformly distributed along the X chromosome. Two-point linkage was assessed using the MLINK and ILINK programs from the LINKAGE package. Markers DXS1223, DXS987, DXS996 and DXS1060 on Xp22 showed consistent linkage to the disease locus with a maximum LOD score of 0.86 at a distance of 22 cM for DXS1060. If further analysis with additional markers and additional family members confirms X-linkage, such a localization would provide support for Lehrke`s hypothesis for X-linkage of major intellectual traits including verbal functioning.

Dunne, P.W.; Doody, R.S.; Epstein, H.F. [Baylor College of Medicine, Houston, TX (United States)] [and others

1994-09-01

153

Application of a sensitive collection heuristic for very large protein families: Evolutionary relationship between adipose triglyceride lipase (ATGL) and classic mammalian lipases  

PubMed Central

Background Manually finding subtle yet statistically significant links to distantly related homologues becomes practically impossible for very populated protein families due to the sheer number of similarity searches to be invoked and analyzed. The unclear evolutionary relationship between classical mammalian lipases and the recently discovered human adipose triglyceride lipase (ATGL; a patatin family member) is an exemplary case for such a problem. Results We describe an unsupervised, sensitive sequence segment collection heuristic suitable for assembling very large protein families. It is based on fan-like expanding, iterative database searches. To prevent inclusion of unrelated hits, additional criteria are introduced: minimal alignment length and overlap with starting sequence segments, finding starting sequences in reciprocal searches, automated filtering for compositional bias and repetitive patterns. This heuristic was implemented as FAMILYSEARCHER in the ANNIE sequence analysis environment and applied to search for protein links between the classical lipase family and the patatin-like group. Conclusion The FAMILYSEARCHER is an efficient tool for tracing distant evolutionary relationships involving large protein families. Although classical lipases and ATGL have no obvious sequence similarity and differ with regard to fold and catalytic mechanism, homology links detected with FAMILYSEARCHER show that they are evolutionarily related. The conserved sequence parts can be narrowed down to an ancestral core module consisting of three ?-strands, one ?-helix and a turn containing the typical nucleophilic serine. Moreover, this ancestral module also appears in numerous enzymes with various substrate specificities, but that critically rely on nucleophilic attack mechanisms. PMID:16551354

Schneider, Georg; Neuberger, Georg; Wildpaner, Michael; Tian, Sun; Berezovsky, Igor; Eisenhaber, Frank

2006-01-01

154

Homozygous familial hypercholesterolemia.  

PubMed

We report a rare case of homozygous familial hypercholesterolemia (HoFH), a 22-year-old Malay woman who presented initially with minor soft tissue injury due to a cycling accident. She was then incidentally found to have severe xanthelasma and hypercholesterolemia (serum TC 15.3 mmol/L and LDL-C 13.9 mmol/L). She was referred to the Specialized Lipid Clinic and was diagnosed with familial hypercholesterolemia (FH) based on the Simon Broome (SB) diagnostic criteria. There was a family history of premature coronary heart disease (CHD) in that three siblings had sudden cardiac death, and of consanguineous marriage in that her parents are cousins. DNA screening of LDLR and APOB genes was done by Polymerase Chain Reaction (PCR), followed by Denaturing High Performance Liquid Chromatography (DHPLC). Homozygous mutation C255S in Exon 5 of her LDLR gene was found. There was no mutation was found in Exon 26 and Exon 29 of the APOB gene. This report is to emphasize the importance of identifying patients with FH and cascade screening through established diagnostic criteria and genetic studies in order to ensure early detection and early treatment intervention to minimize the risk of developing CHD and related complications. PMID:25194536

Alicezah, M K; Razali, R; Rahman, T; Hoh, B P; Suhana, N H; Muid, S; Nawawi, H M; Koshy, M

2014-08-01

155

Familial Isolated Hyperparathyroidism as a Variant of Multiple Endocrine Neoplasia Type 1 in a Large Danish Pedigree  

Microsoft Academic Search

We report here our genetic findings of a family in which 14 mem- bers were affected with isolated primary hyperparathyroidism. Hy- perparathyroidism is the main feature of multiple endocrine neopla- sia type 1 (MEN1), making the recently cloned MEN1 gene a prime candidate gene in this family. Significantly positive lod scores were achieved with D11S4946 (3.36) and D11S4940 (3.53), and

MUSTAPHA KASSEM; TORBEN A. KRUSE; FUNG KI WONG; CATHARINA LARSSON; BIN TEAN TEH

2010-01-01

156

Analysis of BRCA1and BRCA2 large genomic rearrangements in Sri Lankan familial breast cancer patients and at risk individuals  

PubMed Central

Background Majority of mutations found to date in the BRCA1/BRCA2 genes in breast and/or ovarian cancer families are point mutations or small insertions and deletions scattered over the coding sequence and splice junctions. Such mutations and sequence variants of BRCA1 and BRCA2 genes were previously identified in a group of Sri Lankan breast cancer patients. Large genomic rearrangements have been characterized in BRCA1 and BRCA2 genes in several populations but these have not been characterized in Sri Lankan breast cancer patients. Findings A cohort of familial breast cancer patients (N?=?57), at risk individuals (N?=?25) and healthy controls (N?=?23) were analyzed using multiplex ligation-dependent probe amplification method to detect BRCA1 and BRCA2 large genomic rearrangements. One familial breast cancer patient showed an ambiguous deletion in exon 6 of BRCA1 gene. Full sequencing of the ambiguous region was used to confirm MLPA results. Ambiguous deletion detected by MLPA was found to be a false positive result confirming that BRCA1 large genomic rearrangements were absent in the subjects studied. No BRCA2 rearrangement was also identified in the cohort. Conclusion Thus this study demonstrates that BRCA1 and BRCA2 large genomic rearrangements are unlikely to make a significant contribution to aetiology of breast cancer in Sri Lanka. PMID:24906410

2014-01-01

157

Confirmation of X-linked inheritance and provisional mapping of the keratosis follicularis spinulosa decalvans gene on Xp in a large Dutch family.  

PubMed

In a large Dutch family with keratosis follicularis spinulosa decalvans (KFSD, MIM 308800), DNA linkage analysis was performed in order to locate the gene. Pedigree analysis and lod score calculation confirmed X-linked inheritance and revealed significant linkage to DNA markers on Xp. A maximum lod score of 5.70 at theta = 0.0 was obtained with DXS41 (p99.6). The KFSD gene is tentatively located on Xp21.2-p22.2. PMID:1350668

Oosterwijk, J C; Nelen, M; Van Zandvoort, P M; Van Osch, L D; Oranje, A P; Wittebol-Post, D; Van Oost, B A

1992-03-01

158

The politics of school choice in two countries with large private?dependent sectors (Spain and Chile): family strategies, collective action and lobbying  

Microsoft Academic Search

In many countries choice of school is an increasing concern for families and governments. In Spain and Chile, it is also associated with a long?standing political cleavage on the regulation of large sectors of private?dependent schools. This article analyses both the micro? and the macro?politics of choice in these two countries, where low?status 15?year?old students record a significant segregation. At

Xavier Rambla; Óscar Valiente; Carla Frías

2011-01-01

159

Generation of Large Gymnastic Motions for a Family of Under-Actuated Robots by Zero-Moment-Manifold Control  

Microsoft Academic Search

This paper is concerned with a novel control method to generate any desired motion for a family of under-actuated robots such as gymnastics robots and acrobots having a single lower leg pivoted at the floor. This pivotal ankle joint can not be actuator-driven but may have only a passive viscous device such as a rotary damper. Therefore these robots are

Hiroe Hashiguchi; Hiroe Arimoto; Toyohide Sakamoto; Shoji Namikawa

2006-01-01

160

The large soybean (Glycine max) WRKY TF family expanded by segmental duplication events and subsequent divergent selection among subgroups  

PubMed Central

Background WRKY genes encode one of the most abundant groups of transcription factors in higher plants, and its members regulate important biological process such as growth, development, and responses to biotic and abiotic stresses. Although the soybean genome sequence has been published, functional studies on soybean genes still lag behind those of other species. Results We identified a total of 133 WRKY members in the soybean genome. According to structural features of their encoded proteins and to the phylogenetic tree, the soybean WRKY family could be classified into three groups (groups I, II, and III). A majority of WRKY genes (76.7%; 102 of 133) were segmentally duplicated and 13.5% (18 of 133) of the genes were tandemly duplicated. This pattern was not apparent in Arabidopsis or rice. The transcriptome atlas revealed notable differential expression in either transcript abundance or in expression patterns under normal growth conditions, which indicated wide functional divergence in this family. Furthermore, some critical amino acids were detected using DIVERGE v2.0 in specific comparisons, suggesting that these sites have contributed to functional divergence among groups or subgroups. In addition, site model and branch-site model analyses of positive Darwinian selection (PDS) showed that different selection regimes could have affected the evolution of these groups. Sites with high probabilities of having been under PDS were found in groups I, II c, II e, and III. Together, these results contribute to a detailed understanding of the molecular evolution of the WRKY gene family in soybean. Conclusions In this work, all the WRKY genes, which were generated mainly through segmental duplication, were identified in the soybean genome. Moreover, differential expression and functional divergence of the duplicated WRKY genes were two major features of this family throughout their evolutionary history. Positive selection analysis revealed that the different groups have different evolutionary rates. Together, these results contribute to a detailed understanding of the molecular evolution of the WRKY gene family in soybean. PMID:24088323

2013-01-01

161

Novel mutation in TSPAN12 leads to autosomal recessive inheritance of congenital vitreoretinal disease with intra-familial phenotypic variability.  

PubMed

Developmental malformations of the vitreoretinal vasculature are a heterogeneous group of conditions with various modes of inheritance, and include familial exudative vitreoretinopathy (FEVR), persistent fetal vasculature (PFV), and Norrie disease. We investigated a large consanguineous kindred with multiple affected individuals exhibiting variable phenotypes of abnormal vitreoretinal vasculature, consistent with the three above-mentioned conditions and compatible with autosomal recessive inheritance. Exome sequencing identified a novel c.542G?>?T (p.C181F) apparently mutation in the TSPAN12 gene that segregated with the ocular disease in the family. The TSPAN12 gene was previously reported to cause dominant and recessive FEVR, but has not yet been associated with other vitreoretinal manifestations. The intra-familial clinical variability caused by a single mutation in the TSPAN12 gene underscores the complicated phenotype-genotype correlation of mutations in this gene, and suggests that there are additional genetic and environmental factors involved in the complex process of ocular vascularization during embryonic development. Our study supports considering PFV, FEVR, and Norrie disease a spectrum of disorders, with clinical and genetic overlap, caused by mutations in distinct genes acting in the Norrin/?-catenin signaling pathway. PMID:25250762

Gal, Moran; Levanon, Erez Y; Hujeirat, Yasir; Khayat, Morad; Pe'er, Jacob; Shalev, Stavit

2014-12-01

162

Amyloid Goiter Due to Familial Mediterranean Fever in a Patient with Byler Syndrome: A Case Report  

PubMed Central

Background: Familial Mediterranean Fever (FMF), also inherited with autosomal recessive trait, is characterized by recurrent episodes of fever, arthritis, and serositis. Congenital Byler Syndrome (Progressive Familial Intrahepatic Cholestasis) inherited with autosomal recessive trait and characterized by defective secretion of bile acids. FMF associated Amyloid A deposition occurs in many tissues and organs, but amyloid goiter is a rare entity that leads to enlargement and dysfunction of the thyroid. Case Report: We present a rare case of 24 year old male patient who had liver and kidney transplantation due to Byler Syndrome and secondary amyloidosis related to FMF, diagnosed as rapidly growing large amyloid goiter. Deposits of extracellular amyloid and dense adipose metaplasia diagnostic for amyloid goiter are determined upon histopathological examination of thyroidectomy material. Conclusion: When goiter was detected in cases with history of systemic amyloidosis and rapidly growing goitre, amyloid goiter should be remembered at first. This case is unique since two autosomal genetic disorders are together in the same patient and important as it emphasizes the consequences of consanguineous marriage, early diagnosis and treatment compliance of FMF and the awareness of amyloid goiter in patients followed by primary care physicians and healthcare professionals. PMID:25337425

Ci?erli, Özlem; Ünal, Asl? Do?ruk; Par?ldar, Hülya; Demiralay, Ebru; Tarç?n, Özlem

2014-01-01

163

Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population  

PubMed Central

Background Genetics clearly plays a major role in the etiology of autism spectrum disorders (ASDs), but studies to date are only beginning to characterize the causal genetic variants responsible. Until recently, studies using multiple extended multi-generation families to identify ASD risk genes had not been undertaken. Methods We identified haplotypes shared among individuals with ASDs in large multiplex families, followed by targeted DNA capture and sequencing to identify potential causal variants. We also assayed the prevalence of the identified variants in a large ASD case/control population. Results We identified 584 non-conservative missense, nonsense, frameshift and splice site variants that might predispose to autism in our high-risk families. Eleven of these variants were observed to have odds ratios greater than 1.5 in a set of 1,541 unrelated children with autism and 5,785 controls. Three variants, in the RAB11FIP5, ABP1, and JMJD7-PLA2G4B genes, each were observed in a single case and not in any controls. These variants also were not seen in public sequence databases, suggesting that they may be rare causal ASD variants. Twenty-eight additional rare variants were observed only in high-risk ASD families. Collectively, these 39 variants identify 36 genes as ASD risk genes. Segregation of sequence variants and of copy number variants previously detected in these families reveals a complex pattern, with only a RAB11FIP5 variant segregating to all affected individuals in one two-generation pedigree. Some affected individuals were found to have multiple potential risk alleles, including sequence variants and copy number variants (CNVs), suggesting that the high incidence of autism in these families could be best explained by variants at multiple loci. Conclusions Our study is the first to use haplotype sharing to identify familial ASD risk loci. In total, we identified 39 variants in 36 genes that may confer a genetic risk of developing autism. The observation of 11 of these variants in unrelated ASD cases further supports their role as ASD risk variants. PMID:24467814

2014-01-01

164

Skinfold over toenail is pathognomonic for the popliteal pterygium syndrome in a Congolese family with large intrafamilial variability  

PubMed Central

Key Clinical Message We report on three related Congolese popliteal pterygium syndrome (PPS) patients concordant only for the skinfold over the toenail. Mutation analysis revealed that the three affected individuals carried a heterozygous missense mutation in the Exon 4, NM_006147.2:c.250C>T; p.Arg84Cys. This is the first molecularly confirmed PPS family from central Africa. PMID:25548624

Mubungu, Gerrye; Lumaka, Aimé; Matondo, Rosette; Mbayabo, Gloire; Tuka, Deborah; Kayembe, Claudarche; Mulowhe, Didier; Molua, Antoine; Tady, Bruno-Paul; Nkidiaka, Emmanuel; Bunga, Paulo; Lukusa Tshilobo, Prosper; Devriendt, Koenraad

2014-01-01

165

Further evidence that pediatric-onset bipolar disorder comorbid with ADHD represents a distinct subtype: results from a large controlled family study.  

PubMed

We used familial risk analysis to clarify the diagnostic comorbidity between pediatric BP-I disorder and ADHD, testing the hypothesis that pediatric-BP-I disorder comorbid with ADHD represents a distinct subtype. Structured diagnostic interviews were used to obtain DSM-IV psychiatric diagnoses on first-degree relatives (n = 726) of referred children and adolescents satisfying diagnostic criteria for BP-I disorder (n = 239). For comparison, diagnostic information on the first-degree relatives (N = 511) of non-bipolar ADHD children (N = 162) and the first degree relatives (N = 411) of control children (N = 136) with neither ADHD nor BP-I disorder were examined. BP-I disorder and ADHD in probands bred true irrespective of the comorbidity with the other disorder. We also found that the comorbid condition of BP-I disorder plus ADHD also bred true in families, and the two disorders co-segregated among relatives. This large familial risk analysis provides compelling evidence that pediatric BP-I disorder comorbid with ADHD represents a distinct familial subtype. PMID:22979994

Biederman, Joseph; Faraone, Stephen V; Petty, Carter; Martelon, Marykate; Woodworth, K Yvonne; Wozniak, Janet

2013-01-01

166

The hemoglobins of Notothenia angustata, a temperate fish belonging to a family largely endemic to the Antarctic Ocean.  

PubMed

The blood of the teleost Notothenia angustata contains a major hemoglobin (Hb 1, over 95% of the total), accompanied by a minor component (Hb 2). The two hemoglobins have identical beta chains and differ in their alpha chains. The primary structure of both hemoglobins has been established through the elucidation of the complete amino acid sequence of the three chains. The study of the oxygen-binding properties shows that Hb 1 displays the Bohr and Root effects and has high affinity for organic phosphates. N. angustata belongs to the family Nototheniidae, suborder Notothenioidei. Unlike the vast majority of nototheniid species, which live in isolation in the Antarctic Ocean and have developed cold adaptation, N. angustata inhabits the waters of southern New Zealand and is not cold adapted. Although some hematological parameters typically favour oxygen transport in a temperate environment, the hemoglobin multiplicity and structural and functional features closely resemble those of the Antarctic species of the same family and suborder. Thus, N. angustata may be considered as a link between temperate and Antarctic habitats. The hypothetical separation history of N. angustata from the Antarctic species of the same family is discussed in the light of the present findings. PMID:1483479

Fago, A; D'Avino, R; Di Prisco, G

1992-12-15

167

Whole Exome Sequencing Identifies New Causative Mutations in Tunisian Families with Non-Syndromic Deafness  

PubMed Central

Identification of the causative mutations in patients affected by autosomal recessive non syndromic deafness (DFNB forms), is demanding due to genetic heterogeneity. After the exclusion of GJB2 mutations and other mutations previously reported in Tunisian deaf patients, we performed whole exome sequencing in patients affected with severe to profound deafness, from four unrelated consanguineous Tunisian families. Four biallelic non previously reported mutations were identified in three different genes: a nonsense mutation, c.208C>T (p.R70X), in LRTOMT, a missense mutation, c.5417T>C (p.L1806P), in MYO15A and two splice site mutations, c.7395+3G>A, and c.2260+2T>A, in MYO15A and TMC1 respectively. We thereby provide evidence that whole exome sequencing is a powerful, cost-effective screening tool to identify mutations causing recessive deafness in consanguineous families. PMID:24926664

Zainine, Rim; Louha, Malek; Bouyacoub, Yosra; Laroussi, Nadia; Chargui, Mariem; Kefi, Rym; Jonard, Laurence; Dorboz, Imen; Hardelin, Jean-Pierre; Salah, Sihem Belhaj; Levilliers, Jacqueline; Weil, Dominique; McElreavey, Kenneth; Boespflug, Odile Tanguy; Besbes, Ghazi; Abdelhak, Sonia; Petit, Christine

2014-01-01

168

Mutations in SLC29A3, Encoding an Equilibrative Nucleoside Transporter ENT3, Cause a Familial Histiocytosis Syndrome (Faisalabad Histiocytosis) and Familial Rosai-Dorfman Disease  

PubMed Central

The histiocytoses are a heterogeneous group of disorders characterised by an excessive number of histiocytes. In most cases the pathophysiology is unclear and treatment is nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been classed as an autosomal recessively inherited form of histiocytosis with similarities to Rosai-Dorfman disease (RDD) (also known as sinus histiocytosis with massive lymphadenopathy (SHML)). To elucidate the molecular basis of FHC, we performed autozygosity mapping studies in a large consanguineous family and identified a novel locus at chromosome 10q22.1. Mutation analysis of candidate genes within the target interval identified biallelic germline mutations in SLC29A3 in the FHC kindred and in two families reported to have familial RDD. Analysis of SLC29A3 expression during mouse embryogenesis revealed widespread expression by e14.5 with prominent expression in the central nervous system, eye, inner ear, and epithelial tissues including the gastrointestinal tract. SLC29A3 encodes an intracellular equilibrative nucleoside transporter (hENT3) with affinity for adenosine. Recently germline mutations in SLC29A3 were also described in two rare autosomal recessive disorders with overlapping phenotypes: (a) H syndrome (MIM 612391) that is characterised by cutaneous hyperpigmentation and hypertrichosis, hepatomegaly, heart anomalies, hearing loss, and hypogonadism; and (b) PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus) syndrome. Our findings suggest that a variety of clinical diagnoses (H and PHID syndromes, FHC, and familial RDD) can be included in a new diagnostic category of SLC29A3 spectrum disorder. PMID:20140240

Morgan, Neil V.; Morris, Mark R.; Cangul, Hakan; Gleeson, Diane; Straatman-Iwanowska, Anna; Davies, Nicholas; Keenan, Stephen; Pasha, Shanaz; Rahman, Fatimah; Gentle, Dean; Vreeswijk, Maaike P. G.; Devilee, Peter; Knowles, Margaret A.; Ceylaner, Serdar; Trembath, Richard C.; Dalence, Carlos; Kismet, Erol; Köseo?lu, Vedat; Rossbach, Hans-Christoph; Gissen, Paul; Tannahill, David; Maher, Eamonn R.

2010-01-01

169

Immunoglobulin heavy chain variable region and major histocompatibility region genes are linked to induced graves' disease in females from two very large families of recombinant inbred mice.  

PubMed

Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans. PMID:25051451

McLachlan, Sandra M; Aliesky, Holly; Banuelos, Bianca; Magana, Jessica; Williams, Robert W; Rapoport, Basil

2014-10-01

170

Cytogenetic investigations in three cell types of a Saudi family with ataxia telangiectasia  

Microsoft Academic Search

Chromosomal analyses were performed on lymphocytes, fibroblasts and lymphoblastoid cell lines derived from a Saudi family with ataxia telangiectasia (AT). The three siblings of a consanguineous marriage were all affected. The lymphocytes of the AT homozygotes (probands) showed an increase of 2- to 6-fold and 4- to 8-fold respectively, in the frequency of spontaneous and X-ray-induced chromosomal aberrations compared with

Manjula Waghray; Generoso G. Gascon; Sultan Al-Sedairy; Mohammed A. Hannan

1991-01-01

171

Topological properties of large-scale structural brain networks in children with familial risk for reading difficulties  

PubMed Central

Developmental dyslexia is a neurobiological deficit characterized by persistent difficulty in learning to read in children and adults who otherwise possess normal intelligence. Functional and structural connectivity data suggest that developmental dyslexia could be a disconnection syndrome. However, whether abnormalities in connectivity exist in beginning readers at-risk for reading difficulties is unknown. Using graphtheoretical analysis, we investigated differences in global and regional topological properties of structural brain networks in 42 beginning readers with (FH+) and without (FH?) familial risk for reading difficulties. We constructed separate structural correlation networks based on measures of surface area and cortical thickness. Results revealed changes in topological properties in brain regions known to be abnormal in dyslexia (left supramarginal gyrus, left inferior frontal gyrus) in the FH+ group mainly in the network constructed from measures of cortical surface area. We also found alterations in topological properties in regions that are not often advertised as dyslexia but nonetheless play important role in reading (left posterior cingulate, hippocampus, and left precentral gyrus). To our knowledge, this is the first report of altered topological properties of structural correlation networks in children at risk for reading difficulty, and motivates future studies that examine the mechanisms underlying how these brain networks may mediate the influences of family history on reading outcome. PMID:23333415

Hosseini, S.M. Hadi; Black, Jessica M.; Soriano, Teresa; Bugescu, Nicolle; Martinez, Rociel; Raman, Mira M.; Kesler, Shelli R.; Hoeft, Fumiko

2013-01-01

172

Regulatory Patterns of a Large Family of Defensin-Like Genes Expressed in Nodules of Medicago truncatula  

PubMed Central

Root nodules are the symbiotic organ of legumes that house nitrogen-fixing bacteria. Many genes are specifically induced in nodules during the interactions between the host plant and symbiotic rhizobia. Information regarding the regulation of expression for most of these genes is lacking. One of the largest gene families expressed in the nodules of the model legume Medicago truncatula is the nodule cysteine-rich (NCR) group of defensin-like (DEFL) genes. We used a custom Affymetrix microarray to catalog the expression changes of 566 NCRs at different stages of nodule development. Additionally, bacterial mutants were used to understand the importance of the rhizobial partners in induction of NCRs. Expression of early NCRs was detected during the initial infection of rhizobia in nodules and expression continued as nodules became mature. Late NCRs were induced concomitantly with bacteroid development in the nodules. The induction of early and late NCRs was correlated with the number and morphology of rhizobia in the nodule. Conserved 41 to 50 bp motifs identified in the upstream 1,000 bp promoter regions of NCRs were required for promoter activity. These cis-element motifs were found to be unique to the NCR family among all annotated genes in the M. truncatula genome, although they contain sub-regions with clear similarity to known regulatory motifs involved in nodule-specific expression and temporal gene regulation. PMID:23573247

Nallu, Sumitha; Silverstein, Kevin A. T.; Samac, Deborah A.; Bucciarelli, Bruna; Vance, Carroll P.; VandenBosch, Kathryn A.

2013-01-01

173

First evidence of a large CHEK2 duplication involved in cancer predisposition in an Italian family with hereditary breast cancer  

PubMed Central

Background CHEK2 is a multi-cancer susceptibility gene whose common germline mutations are known to contribute to the risk of developing breast and prostate cancer. Case presentation Here, we describe an Italian family with a high number of cases of breast cancer and other types of tumour subjected to the MLPA test to verify the presence of BRCA1, BRCA2 and CHEK2 deletions and duplications. We identified a new 23-kb duplication in the CHEK2 gene extending from intron 5 to 13 that was associated with breast cancer in the family. The presence and localisation of the alteration was confirmed by a second analysis by Next-Generation Sequencing. Conclusions This finding suggests that CHEK2 mutations are heterogeneous and that techniques other than sequencing, such as MLPA, are needed to identify CHEK2 mutations. It also indicates that CHEK2 rare variants, such as duplications, can confer a high susceptibility to cancer development and should thus be studied in depth as most of our knowledge of CHEK2 concerns common mutations. PMID:24986639

2014-01-01

174

A large novel deletion in the APC promoter region causes gene silencing and leads to classical familial adenomatous polyposis in a Manitoba Mennonite kindred.  

PubMed

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by the inheritance of germline mutations in the APC tumour suppressor gene. The vast majority of these are nonsense and frameshift mutations resulting in a truncated protein product and abnormal function. While APC promoter hypermethylation has been previously documented, promoter-specific deletion mutations have not been reported. In a large Canadian Mennonite polyposis kindred, we identified a large novel germline deletion in the APC promoter region by linkage analysis and MLPA. By RT-PCR and sequence analysis, this mutation was found to result in transcriptional silencing of the APC allele. A few genetic disorders have been characterized as over-represented in the Manitoba Mennonite population, however, the incidence of cancer has not been recognized as increased in this population as compared to other Manitoba ethnic groups. This study strengthens the likelihood that this novel APC promoter mutation is linked to this unique population as a founder mutation. PMID:18982352

Charames, George S; Ramyar, Lily; Mitri, Angela; Berk, Terri; Cheng, Hong; Jung, Jack; Bocangel, Patricia; Chodirker, Bernie; Greenberg, Cheryl; Spriggs, Elizabeth; Bapat, Bharati

2008-12-01

175

CD3G gene defects in familial autoimmune thyroiditis.  

PubMed

The patients with CD3? deficiency can present with different clinical findings despite having the same homozygous mutation. We report three new CD3gamma-deficient siblings from a consanguineous family with a combined T-B+NK+ immunodeficiency and their variable clinical and cellular phenotypes despite the same homozygous mutation of the CD3G gene (c.80-1G>C). We also re-evaluate a previously reported non-consanguineous family with two CD3gamma-deficient siblings with the same mutation. The median age at diagnosis was 11 years (14 months-20 years). We found all five patients to display autoimmunity: autoimmune thyroiditis (n = 5), autoimmune haemolytic anaemia (n = 2), immune thrombocytopenia (n = 1), autoimmune hepatitis (n = 1), minimal change nephrotic syndrome (n = 1), vitiligo (n = 1) and positive antinuclear antibodies (n = 3) as well as high IgE (n = 2) and atopic eczema (n = 2). While CD3(+) TCR??+T cell percentages were low in all patients, only one had lymphopenia and 3 had CD3(+) T cell lymphopenia. Strikingly, we report frequent and multiple autoimmunity in tested heterozygous carriers in both families (n = 6; in 67%), and frequent autoimmunity in family members not available for testing (n = 5, in 80%). The results suggest that CD3G should be studied as a candidate gene for autoimmunity and that CD3gamma deficiency should be considered among other primary immunodeficiencies with predominantly autoimmune manifestations. PMID:24910257

Gokturk, B; Keles, S; Kirac, M; Artac, H; Tokgoz, H; Guner, S N; Caliskan, U; Caliskaner, Z; van der Burg, M; van Dongen, J; Morgan, N V; Reisli, I

2014-11-01

176

Correlated Si isotope anomalies and large C-13 enrichments in a family of exotic SiC grains  

NASA Technical Reports Server (NTRS)

A hypothesis is presented to the effect that the distinctive morphological characteristics and comparatively simple Si isotope systematics identify the platy SiC crystals as a genetically related family, formed around a single isotopically heterogeneous presolar star on an association of related stars. The enrichments in C-13 and the Si isotope systematics of the platy SiC are broadly consistent with theoretical models of nucleosynthesis in low-mass, carbon stars on the ASG. The Si isotope array most plausibly reflects mixing between (Si-28)-rich material, inherited from a previous generation of stars, and material enriched in Si-29 and Si-30, produced in intershell regions by neutron capture during He-burning. The absence of a correlation between the Si and C isotopic compositions of the SiC suggests either episodic condensation of SiC, extending over several thermal pulses, in the atmosphere of a single star, or the derivation of the SiC from several stars characterized by different rates of C-13 production.

Stone, J.; Hutcheon, I. D.; Epstein, S.; Wasserburg, G. J.

1991-01-01

177

Inheritance of skewed X chromosome inactivation in a large family with an X-linked recessive deafness syndrome  

SciTech Connect

A new X-linked recessive deafness syndrome was recently reported and mapped to Xq22 (Mohr-Tranebjaeerg syndrome). In addition to deafness, the patients had visual impairment, dystonia, fractures, and mental deterioration. The female carriers did not have any significant manifestations of the syndrome. We examined X chromosome inactivation in 8 obligate and 12 possible carriers by using a polymerase chain reaction analysis of the methylation-dependent amplification of the polymorphic triplet repeat at the androgen receptor locus. Seven of 8 obligate carriers and 1 of 5 carriers by linkage analysis had an extremely skewed pattern in blood DNA not found in 30 normal females. The X inactivation pattern in fibroblast DNA from 2 of the carriers with the extremely skewed pattern was also skewed but to a lesser degree than in blood DNA. One obligate carrier had a random X inactivation pattern in both blood and fibroblast DNA. A selection mechanism for the skewed pattern is therefore not likely. The extremely skewed X inactivation in 8 females of 3 generations in this family may be caused by a single gene that influences skewing of X chromosome inactivation. 22 refs., 2 figs., 1 tab.

Orstavik, K.H.; Orstavik, R.E.; Eiklid, K. [Ulleval Univ. Hospital, Oslo (Norway)] [Ulleval Univ. Hospital, Oslo (Norway); Tranebjaerg, L. [Univ. Hospital, Tromso (Norway)] [Univ. Hospital, Tromso (Norway)

1996-07-12

178

The large-conductance calcium-activated potassium channel holds the key to the conundrum of familial hypokalemic periodic paralysis  

PubMed Central

Purpose Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant channelopathy characterized by episodic attacks of muscle weakness and hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium channel gene, SCN4A, have been found to be responsible for HOKPP; however, the mechanism that causes hypokalemia remains to be determined. The aim of this study was to improve the understanding of this mechanism by investigating the expression of calcium-activated potassium (KCa) channel genes in HOKPP patients. Methods We measured the intracellular calcium concentration with fura-2-acetoxymethyl ester in skeletal muscle cells of HOKPP patients and healthy individuals. We examined the mRNA and protein expression of KCa channel genes (KCNMA1, KCNN1, KCNN2, KCNN3, and KCNN4) in both cell types. Results Patient cells exhibited higher cytosolic calcium levels than normal cells. Quantitative reverse transcription polymerase chain reaction analysis showed that the mRNA levels of the KCa channel genes did not significantly differ between patient and normal cells. However, western blot analysis showed that protein levels of the KCNMA1 gene, which encodes KCa1.1 channels (also called big potassium channels), were significantly lower in the membrane fraction and higher in the cytosolic fraction of patient cells than normal cells. When patient cells were exposed to 50 mM potassium buffer, which was used to induce depolarization, the altered subcellular distribution of BK channels remained unchanged. Conclusion These findings suggest a novel mechanism for the development of hypokalemia and paralysis in HOKPP and demonstrate a connection between disease-associated mutations in calcium/sodium channels and pathogenic changes in nonmutant potassium channels. PMID:25379045

Kim, Sung-Jo; Kang, Sun-Yang; Yi, Jin Woong; Kim, Seung-Min

2014-01-01

179

A Large Family with Carney Complex Caused by the S147G PRKAR1A Mutation Shows a Unique Spectrum of Disease Including Adrenocortical Cancer  

PubMed Central

Context: Most tumors in Carney complex (CNC) are benign, including primary pigmented nodular adrenocortical disease (PPNAD), the main endocrine tumor in CNC. Adrenocortical cancer (AC) has never been observed in the syndrome. Herein, we describe a large Azorean family with CNC caused by a point mutation in the PRKAR1A gene coding for type 1-? (RI?) regulatory subunit of the cAMP-dependent protein kinase A, in which the index patient presented with AC. Objective: We studied the genotype-phenotype correlation in CNC. Design and Setting: We reported on case series and in vitro testing of the PRKAR1A mutation in a tertiary care referral center. Patients: Twenty-two members of a family were investigated for Cushing syndrome and other CNC components; their DNA was sequenced for PRKAR1A mutations. Results: Cushing syndrome due to PPNAD occurred in four patients, including the proposita who presented with AC and three who had Cushing syndrome and/or PPNAD. Lentigines were found in six additional patients who did not have PPNAD. A base substitution (c.439A>G/p.S147G) in PRKAR1A was identified in the proposita, in the three others with PPNAD, in the proposita's twin daughters who had lentigines but no evidence of hypercortisolism, and in five other family members, including one without lentigines or evidence of hypercortisolism. Unlike in other RI? defects, loss of heterozygosity was not observed in AC. The S147G mutation was compared to other expressed PRKAR1A mutations; it led to decreased cAMP and catalytic subunit binding by RI? and increased protein kinase A activity in vitro. Conclusions: In a large family with CNC, one amino acid substitution caused a spectrum of adrenal disease that ranged from lack of manifestations to cancer. PPNAD and AC were the only manifestations of CNC in these patients, in addition to lentigines. These data have implications for counseling patients with CNC and are significant in documenting the first case of AC in the context of PPNAD. PMID:22112814

Anselmo, João; Medeiros, Sandra; Carneiro, Victor; Greene, Elizabeth; Levy, Isaac; Nesterova, Maria; Lyssikatos, Charalampos; Horvath, Anelia; Carney, J. Aidan

2012-01-01

180

Compound Heterozygosity for Two Novel SLC26A4 Mutations in a Large Iranian Pedigree with Pendred Syndrome  

PubMed Central

Objectives The aim of this study was to detect the genetic cause of deafness in a large Iranian family. Due to the importance of SLC26A4 in causing hearing loss, information about the gene mutations can be beneficial in molecular detection and management of deaf patients. Methods We investigated the genetic etiology in a large consanguineous family with 9 deaf patients from Fars province of Iran with no GJB2 mutations. Initially, linkage analysis was performed by four DFNB4 short tandem repeat markers. The result showed linkage to DFNB4 locus. Following that, DNA sequencing of all 21 exons, their adjacent intronic sequences and the promoter of SLC26A4 was carried out for mutation detection. Results Two novel mutations (c.863-864insT and c.881-882delAC) were identified in exon 7 of the gene, in both homozygous and compound heterozygous state in patients. Conclusion Our results supported the importance of the SLC26A4 mutations in the etiology of hearing loss among the Iranian patients and therefore its mutation screening should be considered after GJB2 in the molecular diagnostics of hearing loss, especially when enlarged vestibular aqueduct or goiter is detected. PMID:24353858

Yazdanpanahi, Nasrin; Tabatabaiefar, Mohammad Amin; Farrokhi, Effat; Abdian, Narges; Bagheri, Nader; Shahbazi, Shirin; Noormohammadi, Zahra

2013-01-01

181

Genetics of site specific colon cancer: a family study.  

PubMed

In a kindred of 46 individuals of an Indian Sikh family with no history of consanguinity, 8 suffered from site specific colon (caecum) cancer (not associated with polyposis). The clinical features in the affected kindred were indicative of a "cancer family syndrome". The study of the family depicted an autosomal dominant transmission pattern of site specific colon cancer, with probably 100% penetrance in the affected individuals. A low percentage of mitotic index (MI) was observed in the two probands who were available for the study. No structural or numerical chromosomal aberrations were observed in either case. It is probable that the gene responsible in this family could have begun by mutation at the germ cell level in the 1st generation and remained in a heterozygous condition in the affected individuals. PMID:6088133

Bamezai, R; Singh, G; Khanna, N N; Singh, S

1984-08-01

182

A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly.  

PubMed Central

Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically similar to but genetically distinct from Marfan syndrome. Genetic-linkage analysis has implicated the fibrillin-2 gene (FBN2) as the CCA locus. Mutation analysis of two isolated CCA patients revealed missense mutations, indicating that defects in FBN2 may be responsible for this disorder. However, cosegregation of a mutant allele with the disease phenotype has not yet been established. We have investigated the primary cause of CCA in a large well-characterized kindred with five generations comprising 18 affected individuals. Previous studies demonstrated linkage of this family's CCA phenotype to FBN2. Mutation analysis of cDNA derived from the proband and her affected brother, using a nonisotopic RNase cleavage assay, revealed the partial skipping of exon 31. Approximately 25% mutant transcript is produced, which is apparently sufficient to cause a CCA phenotype. Sequence analysis of genomic DNA revealed an unusual base composition for intron 30 and identified the mutation, a g-26t transversion, in the vicinity of the splicing branch-point site in intron 30. Genomic DNA from 30 additional family members, both affected and unaffected, then was analyzed for the mutation. The results clearly demonstrate cosegregation of the branch-point mutation with the CCA phenotype. This is the first report of a CCA mutation in a multiplex family, unequivocally establishing that mutation in FBN2 are responsible for the CCA phenotype. In addition, branch-point mutations only very rarely have been associated with human disease, suggesting that the unusual composition of this intron influences splicing stability. Images Figure 2ab Figure 2c Figure 3ab Figure 3c Figure 4 Figure 6 Figure 7 PMID:9199560

Maslen, C; Babcock, D; Raghunath, M; Steinmann, B

1997-01-01

183

Correlated Si isotope anomalies and large 13C enrichments in a family of exotic SiC grains.  

PubMed

A suite of morphologically distinctive silicon carbide (SiC) grains from the Orgueil and Murchison carbonaceous chondrite meteorites contains Si and C of highly anomalous isotopic composition. All of the SiC grains in this suite are characterized by a distinctive platy morphology and roughly developed hexagonal crystal forms that allow them to be distinguished from other types of SiC found in the host meteorites. The delta 29Si and delta 30Si values of individual SiC crystals deviate from those of normal solar material by more than 100%, while the delta 13C values range from 150 to 5200%. Isotopically normal C and Si are not found in any of these SiC crystals. The SiC grains belonging to this morphological suite are isotopically distinct from fine-grained SiC aggregates and other morphological types of SiC in unequilibrated meteorites. The 29Si/28Si and 30Si/28Si ratios of these platy grains are well correlated and define a linear array that does not pass through the composition of normal, solar Si. This behavior contrasts sharply with the diverse and poorly correlated Si isotopic compositions shown by the total SiC population. We suggest that the distinctive morphological characteristics and comparatively simple Si isotope systematics identify the platy SiC crystals as a genetically related family, formed around a single, isotopically heterogeneous presolar star or an association of related stars. The enrichments in 13C and the Si isotope systematics of the platy SiC are broadly consistent with theoretical models of nucleosynthesis in low-mass, carbon stars on the asymptotic giant branch. The Si isotope array most plausibly reflects mixing between 28Si-rich material, inherited from a previous generation of stars, and material enriched in 29Si and 30Si, produced in intershell regions by neutron capture during He-burning. 13C is also produced in intershell regions by proton reactions on 12C seed nuclei and is carried with s-process nuclei to the stellar envelope by convection which penetrates down to the He shell. The absence of a correlation between the Si and C isotopic compositions of the SiC suggests either episodic condensation of SiC, extending over several thermal pulses, in the atmosphere of a single star, or derivation of the SiC from several stars characterized by different rates of 13C production. In the multiple star scenario, the linear correlation of the 29Si/28Si and 30Si/28Si ratios among the platy SiC indicates that these stars evolved from a common Si seed composition under similar conditions of neutron-capture nucleosynthesis. The 29Si/30Si ratio of the SiC, inferred by us to be produced by neutron capture in the stellar interior, is distinct from values calculated from models of nucleosynthesis in AGB stars. PMID:11538380

Stone, J; Hutcheon, I D; Epstein, S; Wasserburg, G J

1991-01-01

184

Heritability of determinants of the metabolic syndrome among healthy Arabs of the Oman family study.  

PubMed

The metabolic syndrome, as defined by the International Diabetes Federation, was investigated in five large, extended, highly consanguineous, healthy Omani Arab families of a total of 1277 individuals. Heritability (h2) of the phenotypic abnormalities that make up the syndrome and other related traits was estimated by variance decomposition method using SOLAR software. The overall prevalence of the syndrome was 23%. The prevalence of abnormalities making the syndrome in a descending order were: obligatory waist circumference, hypertension, raised fasting blood glucose, low serum high-density lipoprotein (HDL), and raised serum triglycerides (TGs). Highly significant, but widely spread, h2 values were obtained for: height (0.68), weight (0.68), BMI (0.68), serum HDL (0.63), serum leptin (0.55), percentage body fat (0.53), total serum cholesterol (0.53), fasting serum insulin (0.51), homeostasis model assessment-insulin resistance index (0.48), serum TG (0.43), waist circumference (0.40), diastolic blood pressure (0.38), and 2-hour glucose level (0.17), whereas for the metabolic syndrome itself, h2 was 0.38. The wide spread of h2 results (0.07 to 0.68) indicates that some determinants, such as weight, BMI, and HDL level, are under significant genetic influence among the Omani Arabs. Other determinants such as insulin resistance, abdominal obesity, diastolic blood pressure, and TG levels seem to be more environmentally driven. PMID:17372303

Bayoumi, Riad A; Al-Yahyaee, Saeed A S; Albarwani, Sulayma A; Rizvi, Syed G; Al-Hadabi, Saleh; Al-Ubaidi, Firial F; Al-Hinai, Ali T; Al-Kindi, Mohammed N; Adnan, Haleema T; Al-Barwany, Hameeda S; Comuzzie, Antony G; Cai, Guowen; Lopez-Alvarenga, Juan C; Hassan, Mohammed O

2007-03-01

185

The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene  

PubMed Central

Background Members of the makorin (mkrn) gene family encode RING/C3H zinc finger proteins with U3 ubiquitin ligase activity. Although these proteins have been described in a variety of eukaryotes such as plants, fungi, invertebrates and vertebrates including human, almost nothing is known about their structural and functional evolution. Results Via partial sequencing of a testis cDNA library from the poeciliid fish Xiphophorus maculatus, we have identified a new member of the makorin gene family, that we called mkrn4. In addition to the already described mkrn1 and mkrn2, mkrn4 is the third example of a makorin gene present in both tetrapods and ray-finned fish. However, this gene was not detected in mouse and rat, suggesting its loss in the lineage leading to rodent murids. Mkrn2 and mkrn4 are located in large ancient duplicated regions in tetrapod and fish genomes, suggesting the possible involvement of ancestral vertebrate-specific genome duplication in the formation of these genes. Intriguingly, many mkrn1 and mkrn2 intronless retrocopies have been detected in mammals but not in other vertebrates, most of them corresponding to pseudogenes. The nature and number of zinc fingers were found to be conserved in Mkrn1 and Mkrn2 but much more variable in Mkrn4, with lineage-specific differences. RT-qPCR analysis demonstrated a highly gonad-biased expression pattern for makorin genes in medaka and zebrafish (ray-finned fishes) and amphibians, but a strong relaxation of this specificity in birds and mammals. All three mkrn genes were maternally expressed before zygotic genome activation in both medaka and zebrafish early embryos. Conclusion Our analysis demonstrates that the makorin gene family has evolved through large-scale duplication and subsequent lineage-specific retroposition-mediated duplications in vertebrates. From the three major vertebrate mkrn genes, mkrn4 shows the highest evolutionary dynamics, with lineage-specific loss of zinc fingers and even complete gene elimination from certain groups of vertebrates. Comparative expression analysis strongly suggests that the ancestral E3 ubiquitin ligase function of the single copy mkrn gene before duplication in vertebrates was gonad-specific, with maternal expression in early embryos. PMID:21172006

2010-01-01

186

The Community of Family Circles (CFC) algorithm: a new inversion approach to obtaining self-consitent 4D thermal histories from large, spatially distributed thermochronological data sets  

NASA Astrophysics Data System (ADS)

One of the most significant advances in interpreting thermochronological data is arguably our ability to extract information about the rate and trajectory of cooling over a range of temperatures, rather than having to rely on the veracity of the simplification of assuming a single closure temperature specified by a rate of monotonic cooling. Modern thermochronometry data, such as apatite fission track and (U-Th)/He analysis, are particularly good examples of data amenable to this treatment as acceptably well calibrated kinetic models now exist for both systems. With ever larger data sets of this type being generated over ever larger areas the prospect of inverting very large amounts of such data distributed spatially over large areas offers new possibilities for constraining the thermal and erosional histories over length scales approximating whole orogens and sub-continents. The challenge though is in how to properly deal with joint inversion of multiple samples in a self-consistent manner while also utilising all the available information contained in the data. We describe a new approach to this problem, called the Community of Family Circles (CFC) algorithm, which extracts information from spatially distributed apatite fission track ages (AFT) and track length distributions (TLD). The method is based on the rationale that the 3D geothermal field of the crust varies smoothly through space and time because of the efficiency of thermal diffusion. Our approach consists of seeking groups of spatially adjacent samples, or families, within a given circular radius for which a common thermal history is appropriate. The temperature offsets between individual time-temperature paths are determined relative to a low-pass filtered topographic surface, whose shape is assumed to mimic the shape of the isotherms in the partial annealing zone. This enables a single common thermal history to be shared, or interpolated, between the family members while still honouring the individual samples temperature offset requirements. The geothermal gradient can be either treated as a parameter in the inversion scheme or evaluated when local vertical profile or heat flow measurements are available. As data for each sample is inverted several times with different subsets, or as a member of different families, we then extract the subset with the lowest misfit and assign that sample to its respective ''family'' whose optimum time-temperature path is subsequently assigned to the sample. We thus obtain a set of thermal histories (one for each sample) which can then be interpolated to obtain exhumation rates or maximum temperature maps. We demonstrate our approach on a variety of synthetic datasets, generated for different geomorphologies and sampling densities, using the 3D thermal Pecube code in order to test the resolution and limits of the method. The approach is then applied to a 600 by 600 km area in northern Namibia where an extensive apatite fission track dataset including ages and track length distributions is available. We finally discuss extension of the technique to multiple thermochronometers. We also discuss possible future modifications and strategies for improving the flexibility and computational efficiency and effectiveness of the method.

Beucher, R.; Brown, R. W.

2013-12-01

187

Comparative Analysis of P450 Signature Motifs EXXR and CXG in the Large and Diverse Kingdom of Fungi: Identification of Evolutionarily Conserved Amino Acid Patterns Characteristic of P450 Family  

PubMed Central

Cytochrome P450 monooxygenases (P450s) are heme-thiolate proteins distributed across the biological kingdoms. P450s are catalytically versatile and play key roles in organisms primary and secondary metabolism. Identification of P450s across the biological kingdoms depends largely on the identification of two P450 signature motifs, EXXR and CXG, in the protein sequence. Once a putative protein has been identified as P450, it will be assigned to a family and subfamily based on the criteria that P450s within a family share more than 40% homology and members of subfamilies share more than 55% homology. However, to date, no evidence has been presented that can distinguish members of a P450 family. Here, for the first time we report the identification of EXXR- and CXG-motifs-based amino acid patterns that are characteristic of the P450 family. Analysis of P450 signature motifs in the under-explored fungal P450s from four different phyla, ascomycota, basidiomycota, zygomycota and chytridiomycota, indicated that the EXXR motif is highly variable and the CXG motif is somewhat variable. The amino acids threonine and leucine are preferred as second and third amino acids in the EXXR motif and proline and glycine are preferred as second and third amino acids in the CXG motif in fungal P450s. Analysis of 67 P450 families from biological kingdoms such as plants, animals, bacteria and fungi showed conservation of a set of amino acid patterns characteristic of a particular P450 family in EXXR and CXG motifs. This suggests that during the divergence of P450 families from a common ancestor these amino acids patterns evolve and are retained in each P450 family as a signature of that family. The role of amino acid patterns characteristic of a P450 family in the structural and/or functional aspects of members of the P450 family is a topic for future research. PMID:24743800

Syed, Khajamohiddin; Mashele, Samson Sitheni

2014-01-01

188

A missense mutation in the alpha-actinin 1 gene (ACTN1) is the cause of autosomal dominant macrothrombocytopenia in a large French family.  

PubMed

Inherited thrombocytopenia is a heterogeneous group of disorders characterized by a reduced number of blood platelets. Despite the identification of nearly 20 causative genes in the past decade, approximately half of all subjects with inherited thrombocytopenia still remain unexplained in terms of the underlying pathogenic mechanisms. Here we report a six-generation French pedigree with an autosomal dominant mode of inheritance and the identification of its genetic basis. Of the 55 subjects available for analysis, 26 were diagnosed with isolated macrothrombocytopenia. Genome-wide linkage analysis mapped a 10.9 Mb locus to chromosome 14 (14q22) with a LOD score of 7.6. Candidate gene analysis complemented by targeted next-generation sequencing identified a missense mutation (c.137GA; p.Arg46Gln) in the alpha-actinin 1 gene (ACTN1) that segregated with macrothrombocytopenia in this large pedigree. The missense mutation occurred within actin-binding domain of alpha-actinin 1, a functionally critical domain that crosslinks actin filaments into bundles. The evaluation of cultured mutation-harboring megakaryocytes by electron microscopy and the immunofluorescence examination of transfected COS-7 cells suggested that the mutation causes disorganization of the cellular cytoplasm. Our study concurred with a recently published whole-exome sequence analysis of six small Japanese families with congenital macrothrombocytopenia, adding ACTN1 to the growing list of thrombocytopenia genes. PMID:24069336

Guéguen, Paul; Rouault, Karen; Chen, Jian-Min; Raguénès, Odile; Fichou, Yann; Hardy, Elisabeth; Gobin, Eric; Pan-Petesch, Brigitte; Kerbiriou, Mathieu; Trouvé, Pascal; Marcorelles, Pascale; Abgrall, Jean-Francois; Le Maréchal, Cédric; Férec, Claude

2013-01-01

189

A Missense Mutation in the Alpha-Actinin 1 Gene (ACTN1) Is the Cause of Autosomal Dominant Macrothrombocytopenia in a Large French Family  

PubMed Central

Inherited thrombocytopenia is a heterogeneous group of disorders characterized by a reduced number of blood platelets. Despite the identification of nearly 20 causative genes in the past decade, approximately half of all subjects with inherited thrombocytopenia still remain unexplained in terms of the underlying pathogenic mechanisms. Here we report a six-generation French pedigree with an autosomal dominant mode of inheritance and the identification of its genetic basis. Of the 55 subjects available for analysis, 26 were diagnosed with isolated macrothrombocytopenia. Genome-wide linkage analysis mapped a 10.9 Mb locus to chromosome 14 (14q22) with a LOD score of 7.6. Candidate gene analysis complemented by targeted next-generation sequencing identified a missense mutation (c.137GA; p.Arg46Gln) in the alpha-actinin 1 gene (ACTN1) that segregated with macrothrombocytopenia in this large pedigree. The missense mutation occurred within actin-binding domain of alpha-actinin 1, a functionally critical domain that crosslinks actin filaments into bundles. The evaluation of cultured mutation-harboring megakaryocytes by electron microscopy and the immunofluorescence examination of transfected COS-7 cells suggested that the mutation causes disorganization of the cellular cytoplasm. Our study concurred with a recently published whole-exome sequence analysis of six small Japanese families with congenital macrothrombocytopenia, adding ACTN1 to the growing list of thrombocytopenia genes. PMID:24069336

Guéguen, Paul; Rouault, Karen; Chen, Jian-Min; Raguénès, Odile; Fichou, Yann; Hardy, Elisabeth; Gobin, Eric; Pan-petesch, Brigitte; Kerbiriou, Mathieu; Trouvé, Pascal; Marcorelles, Pascale; Abgrall, Jean-francois; Le Maréchal, Cédric; Férec, Claude

2013-01-01

190

Human KZNF Gene Catalog - A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors  

DOE Data Explorer

Kruppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotes. KRAB-ZNF proteins, in which a potent repressor domain is attached to a tandem array of DNA-binding zinc-finger motifs, are specific to tetrapod vertebrates and represent the largest class of ZNF proteins in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the genome sequence for key motifs and then constructed and manually curated gene models incorporating those sequences. The resulting gene catalog contains 423 KRAB-ZNF protein-coding loci, yielding alternative transcripts that altogether predict at least 742 structurally distinct proteins. Active rounds of segmental duplication, involving single genes or larger regions and including both tandem and distributed duplication events, have driven the expansion of this mammalian gene family. Comparisons between the human genes and ZNF loci mined from the draft mouse, dog, and chimpanzee genomes not only identified 103 KRAB-ZNF genes that are conserved in mammals but also highlighted a substantial level of lineage-specific change; at least 136 KRAB-ZNF coding genes are primate specific, including many recent duplicates. KRAB-ZNF genes are widely expressed and clustered genes are typically not coregulated, indicating that paralogs have evolved to fill roles in many different biological processes. To facilitate further study, we have developed a Web-based public resource with access to gene models, sequences, and other data, including visualization tools to provide genomic context and interaction with other public data sets. [This abstract was copied from: S Huntley, DM Baggott, AT Hamilton, M Tran-Gyamfi, S Yang, J Kim, L Gordon, E Branscomb, and L Stubbs. 2006. A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors, Genome Research 16(5):669 - 677] The website provides the ability to search the online catalog by genomic coordinates, name, locus type, and motifs, to utilize a graphical browser and to download data files.

Huntley, S; Baggott, D.M.; Hamilton, A.T.; Tran-Gyamfi, M.; Yang, S.; Kim, J.; Gordon, L.; Branscomb, E.; Stubbs, L.

191

Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q  

SciTech Connect

Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North American kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.

Fink, J.K.; Wu, C.T.B.; Jones, S.M.

1994-09-01

192

Effects of atorvastatin on fasting plasma and marginated apolipoproteins B48 and B100 in large, triglyceride-rich lipoproteins in familial combined hyperlipidemia.  

PubMed

Large triglyceride (TG)-rich lipoproteins (TRLs) circulate in the blood, but they may also be present in a marginated pool, probably attached to the endothelium. It is unknown whether statins can influence this marginated pool in vivo in humans. Intravenous fat tests were performed in familial combined hyperlipidemia (FCHL) subjects before and after atorvastatin treatment and in controls to investigate whether acute increases in apoB in TRL fractions would occur, potentially reflecting the release of this TRL from a marginated pool. After a 12-h fast, a bolus injection of 10% Intralipid was given to 12 FCHL patients before and after 16-wk treatment with atorvastatin. Twelve carefully matched controls were included. For 60 min postinjection, apoB48, apoB100, and lipids were measured in TRLs. Fasting apoB100 in all TRL fractions were 2- to 3-fold higher in untreated FCHL compared with controls. ApoB48 concentrations in chylomicron fractions increased significantly within 10 min in FCHL before and after treatment, but not in controls. ApoB100 increased significantly in the chylomicron fractions in untreated FCHL and in controls, but not in FCHL after treatment. In very low density lipoprotein 1, apoB100 increased only in untreated FCHL. In very low density lipoprotein 2, apoB100 did not change in any group. These data show that increasing the number of circulating TRLs by chylomicron-like particles, results in increased plasma apoB-TRLs, probably by acute release from a marginated pool. This is a physiological process occurring in FCHL and in healthy normolipidemic subjects, but it is more pronounced in the former. Decreased marginated TRL particles in FCHL is a novel antiatherogenic property of atorvastatin. PMID:15472200

Verseyden, C; Meijssen, S; Cabezas, M Castro

2004-10-01

193

A Novel Splice-Site Mutation in ALS2 Establishes the Diagnosis of Juvenile Amyotrophic Lateral Sclerosis in a Family with Early Onset Anarthria and Generalized Dystonias  

PubMed Central

The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS), one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes. PMID:25474699

Vu, Anthony; Azim, Saad; Silver, David L.; Mansoor, Atika; Tay, Stacey Kiat Hong; Abbasi, Sumiya; Hashmi, Asraf Hussain; Janjua, Jamal; Khalid, Sumbal; Tai, E. Shyong; Yeo, Gene W.; Khor, Chiea Chuen

2014-01-01

194

Families with Daughters, Families with Sons: Different Challenges for Family Relationships and Marital Satisfaction?  

Microsoft Academic Search

In a longitudinal study, the links between family relations and marital relations were examined in families with early adolescent children. Over the course of 4 years, 128 mother–father–adolescent triads were investigated annually. They completed questionnaires assessing family climate and marital relationships. Longitudinal analyses revealed that the initially large discrepancies between adolescents' and their parents' perceptions of family cohesion, support, and

Inge Seiffge-Krenke

1999-01-01

195

Truncation of the E3 ubiquitin ligase component FBXO31 causes non-syndromic autosomal recessive intellectual disability in a Pakistani family.  

PubMed

In this study, we have performed autozygosity mapping on a large consanguineous Pakistani family segregating with intellectual disability. We identified two large regions of homozygosity-by-descent (HBD) on 16q12.2-q21 and 16q24.1-q24.3. Whole exome sequencing (WES) was performed on an affected individual from the family, but initially, no obvious mutation was detected. However, three genes within the HBD regions that were not fully captured during the WES were Sanger sequenced and we identified a five base pair deletion (actually six base pairs deleted plus one base pair inserted) in exon 7 of the gene FBXO31. The variant segregated completely in the family, in recessive fashion giving a LOD score of 3.95. This variant leads to a frameshift and a premature stop codon and truncation of the FBXO31 protein, p.(Cys283Asnfs*81). Quantification of mRNA and protein expression suggests that nonsense-mediated mRNA decay also contributes to the loss of FBXO31 protein in affected individuals. FBXO31 functions as a centrosomal E3 ubiquitin ligase, in association with SKP1 and Cullin-1, involved in ubiquitination of proteins targeted for degradation. The FBXO31/SKP1/Cullin1 complex is important for neuronal morphogenesis and axonal identity. FBXO31 also plays a role in dendrite growth and neuronal migration in developing cerebellar cortex. Our finding adds further evidence of the involvement of disruption of the protein ubiquitination pathway in intellectual disability. PMID:24623383

Mir, Asif; Sritharan, Kumudesh; Mittal, Kirti; Vasli, Nasim; Araujo, Carolina; Jamil, Talal; Rafiq, Muhammad Arshad; Anwar, Zubair; Mikhailov, Anna; Rauf, Sobiah; Mahmood, Huda; Shakoor, Abdul; Ali, Sabir; So, Joyce; Naeem, Farooq; Ayub, Muhammad; Vincent, John B

2014-08-01

196

Autosomal dominant Kufs` disease: Clinical heterogeneity in nine families, and exclusion of linkage to CLN1 and CLN3 markers in a large American kindred  

SciTech Connect

Most forms of neuronal ceroid lipofuscinosis (NCL) are autosomal recessive, and three genes have already been mapped: the infantile form (CLN 1); the juvenile form (CLN 3); and the early juvenile variant (CLN 5) on chromosomes 1, 16 and 13, respectively. Kufs` disease or adolescent-adult onset NCL is usually inherited as an autosomal recessive trait, and presents as three distinct clinical syndromes: progressive myoclonus epilepsy (PME) with onset in the early teens or around age 30; and onset of dementia with motor disability in the 30s. We have studied three families originating from different parts of the USA manifesting dominantly inherited Kufs` disease. Granular osmophilic deposits (GROD) were found in brain, but storage in skin was not an obligatory feature. Six dominantly inherited PME families have been ascertained from three different regions of Spain. No storage was found in skin or muscle in any of these families. The mean age of onset in the American families is earlier, the clinical manifestations more severe, and the progression much more rapid that in the Spanish families. These findings would suggest the possibility of genetic heterogeneity involving two or more loci, or different mutations at the same gene locus. Genetic linkage studies have been carried out in a six-generation New Jersey family in an attempt to characterize the gene(s) responsible for this disorder. The infantile NCL locus on chromosome 1p (CLN1) and the juvenile NCL locus on chromosome 16p (CLN 3) have been excluded in this family. Further clinical, pathological and molecular genetic studies should lead to the clarification of the diagnostic approaches in this disorder.

Andermann, F.; Andermann, E.; Carpenter, S. [and others

1994-09-01

197

Family Folklore  

ERIC Educational Resources Information Center

Discusses the Family Folklore Program of the Smithsonian Institution's annual Festival of American Folklife, in which the whole family can be involved in tracing family history through story telling, photographs, etc. (MS)

Kotkin, Amy J.; Baker, Holly C.

1977-01-01

198

Foster Families  

MedlinePLUS

... foster family? Let's find out. What Are Foster Families? The word "foster" means to help someone (or ... home. Continue Why Do Kids Live With Foster Families? Most often, a kid goes into a foster ...

199

Family History  

MedlinePLUS

Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

200

Family Functioning in Neglectful Families.  

ERIC Educational Resources Information Center

Comparison of family functioning in 103 neglectful and 102 nonneglectful low-income families found that neglectful mothers reported their families as having more family conflict and less expression of feelings, but not less cohesiveness. Observational measures indicated neglectful families were less organized, more chaotic, and less verbally…

Gaudin, James M., Jr.; And Others

1996-01-01

201

Vocal cord and diaphragm paralysis, as clinical features of a French family with autosomal recessive Charot-Marie-Tooth disease, associated with a new mutation in the GDAP1 gene  

Microsoft Academic Search

Axonal forms of Charot-Marie-Tooth disease, either dominantly or recessively inherited, are clinically and genetically heterogeneous. We describe the clinical and electrophysiological characteristics of an axonal autosomal recessive form of Charot-Marie-Tooth disease in a French family, associated with a new mutation of the ganglioside-induced differentiation-associated protein-1 gene (GDAP1). Two sisters, born to non-consanguineous parents, presented severe proximal and distal sensorimotor deficit,

Tanya Stojkovic; Philippe Latour; Ghislaine Viet; Jérôme de Seze; Jean-François Hurtevent; Antoon Vandenberghe; P. Vermersch

2004-01-01

202

Familiality of Tourette Syndrome, Obsessive-Compulsive Disorder, and Attention-Deficit/Hyperactivity Disorder: Heritability Analysis in a Large Sib-Pair Sample  

ERIC Educational Resources Information Center

Objective: Tourette syndrome (TS) is a neuropsychiatric disorder with a genetic component that is highly comorbid with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). However, the genetic relations between these disorders have not been clearly elucidated. This study examined the familial relations among TS,…

Mathews, Carol A.; Grados, Marco A.

2011-01-01

203

Family functioning in neglectful families  

Microsoft Academic Search

Family functioning in 103 neglectful and 102 non-neglectful low-income families is examined using self-report and observational measures. Neglectful mothers reported their families as having more family conflict and less expression of feelings, but not less cohesive. Ratings of observed and videotaped family interactions indicated neglect families were less organized, more chaotic, less verbally expressive, showed less positive and more negative

James M. Gaudin; Norman A. Polansky; Allie C. Kilpatrick; Paula Shilton

1996-01-01

204

Attitudes towards people with mental illness among psychiatrists, psychiatric nurses, involved family members and the general population in a large city in Guangzhou, China  

PubMed Central

Purpose Stigma towards people with mental illness is believed to be widespread in low and middle income countries. Methods This study assessed the attitudes towards people with mental illness among psychiatrists, psychiatric nurses, involved family members of patients in a psychiatric facility and the general public using a standard 43-item survey (N?=?535). Exploratory factor analysis identified four distinctive attitudes which were then compared using Analysis of Covariance (ANCOVA) among the four groups, all with ties to the largest psychiatric facility in Guangzhou, China, adjusting for sociodemographic differences. Results Four uncorrelated factors expressed preferences for 1) community-based treatment, social integration and a biopsychosocial model of causation, 2) direct personal relationships with people with mental illness, 3) a lack of fear and positive views of personal interactions with people with mental illness, 4) disbelief in superstitious explanations of mental illness. Statistically significant differences favored community-based treatment and biopsychosocial causation (factor 1) among professional groups (psychiatrists and nurses) as compared with family members and the general public (p?family members, unexpectedly, showed far weaker personal preferences for direct personal relationships with people with mental illness than all three other groups (p?family members showed the least positive attitudes towards direct personal relationships with people with mental illness. These findings suggest support for a more extensive, formal system of care that gives family members some distance from the problems of their relatives and support in their care. PMID:25053975

2014-01-01

205

[Family Involvement.  

ERIC Educational Resources Information Center

This theme issue provides four articles that address family involvement in the transition of youth with disabilities from school to work. The first article, "Family Involvement" by Marge Goldberg and Shauna McDonald, offers evidence of the importance of family involvement at this stage of the individual's life, reports on families' experiences,…

Alliance: The Newsletter of the National Transition Alliance, 1996

1996-01-01

206

Family Privilege  

ERIC Educational Resources Information Center

Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

Seita, John R.

2014-01-01

207

Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in a large multi-generation family.  

PubMed

Developmental dysplasia of the hip (DDH) is a crippling condition that affects children and adults, with an average incidence of 1-1.5 cases per 1000 live births. It results in disabling arthritis of the hip in up to 60% patients in the 20-40 year age group. There is no accurate diagnostic test available for newborns. The purpose of our study is to develop a sensitive and specific genetic test for DDH by identifying causative mutations. Linkage analysis and whole exome sequencing of 4 severely affected individuals of a 4 generation 71 member family was performed. The damaging rs3732378 variant in the CX3CR1 chemokine receptor was shared by all affected family members and by 15% of 28 sporadic dysplastics. PMID:24998320

Feldman, George J; Parvizi, Javad; Sawan, Hind; Erickson, Jill A; Peters, Christopher L

2014-09-01

208

Chilo iridescent virus encodes a putative helicase belonging to a distinct family within the “Dead\\/H” superfamily: Implications for the evolution of large DNA viruses  

Microsoft Academic Search

The complete nucleotide sequence of theEcoRI DNA fragment M (7099 bp; 0.310–0.345 map units) of the genome of insect iridescent virus type 6—Chilo iridescent virus (CIV)—was determined. A 606 codon open reading frame located in this region encoded a protein (p69) related to a distinct family of putative DNA and\\/or RNA helicases belonging to the “DEAD\\/H” superfamily. Unique sequence signatures

Kai-Christian Sonntag; Paul Schnitzler; Eugene V. Koonin; Gholamreza Darai

1994-01-01

209

The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene  

Microsoft Academic Search

BACKGROUND: Members of the makorin (mkrn) gene family encode RING\\/C3H zinc finger proteins with U3 ubiquitin ligase activity. Although these proteins have been described in a variety of eukaryotes such as plants, fungi, invertebrates and vertebrates including human, almost nothing is known about their structural and functional evolution. RESULTS: Via partial sequencing of a testis cDNA library from the poeciliid

Astrid Böhne; Amandine Darras; Helena D'Cotta; Jean-Francois Baroiller; Delphine Galiana-Arnoux; Jean-Nicolas Volff

2010-01-01

210

Two large Arabidopsis thaliana gene families are homologous to the Brassica gene superfamily that encodes pollen coat proteins and the male component of the self-incompatibility response  

Microsoft Academic Search

The male component of the self-incompatibility response in Brassica has recently been shown to be encoded by the S locus cysteine-rich gene (SCR). SCR is related, at the sequence level, to the pollen coat protein (PCP) gene family whose members encode small, cysteine-rich proteins located in the proteo-lipidic surface layer (tryphine) of Brassica pollen grains. Here we show that the

Vincent Vanoosthuyse; Christine Miege; Christian Dumas; J. Mark Cock

2001-01-01

211

Severe mental retardation in six generations of a large South African family carrying a translocation t(6;10)(q27;q25.2).  

PubMed Central

Partial monosomy 10q25.2----qter, detected in a newborn baby with multiple congenital abnormalities, was found to be derived from a balanced maternal translocation t(6;10)(q27;q25.2). The pedigree of six generations of the family is presented. In an extensive cytogenetic study of this family, the chromosome complements of 57 subjects, potentially capable of carrying some form of this translocation, were analysed. A total of 14 male carriers (four obligatory) and 14 female carriers (three obligatory) of this translocation was found. Partial trisomy 10q25.2----qter, associated with severe mental retardation, occurred in nine cases, eight males and one female. Two of these eight males were detected prenatally and subsequently therapeutically aborted. The phenotypes of the family members with partial trisomy 10q25.2----qter are compared to each other and to those reported in publications. No further cases of partial monosomy 10q25.2----qter were encountered. A review of published reports of partial monosomy and partial trisomy 10qter is given. The apparent absence of infertility, the occurrence of many first trimester miscarriages, and the marked sex ratio are discussed. Images PMID:3783620

Brusnický, J; van Heerden, K M; de Jong, G; Cronjé, A S; Retief, A E

1986-01-01

212

Family Governance with Family Councils  

Microsoft Academic Search

From the third generation onwards, family firms could get into business threatening situations. This might depend on the growing number of owners, the increasing distance of family members from the firm, and the heterogeneity of their interests. Thus, agency prob- lems and negative conflicts might occur. This calls for the appropriate choice of family gov- ernance mechanisms. Family councils might

Klaus Brockhoff; Alexander Koeberle-Schmid

213

Family Violence and Family Physicians  

PubMed Central

The acronym IDEALS summarizes family physicians' obligations when violence is suspected: to identify family violence; document injuries; educate families and ensure safety for victims; access resources and coordinate care; co-operate in the legal process; and provide support for families. Failure to respond reflects personal and professional experience and attitudes, fear of legal involvement, and lack of knowledge. Risks of intervention include physician burnout, physician overfunctioning, escalation of violence, and family disruption. PMID:21228987

Herbert, Carol P.

1991-01-01

214

Familial Amyloidosis Cutis Dyschromica in Three Siblings: Report from Indonesia  

PubMed Central

Amyloidosis cutis dyschromica (ACD) is an extremely rare type of primary cutaneous amyloidosis. To date there are fewer than 40 published cases worldwide; some were reported affecting several family members. Its resemblance to other common pigmentation disorders makes it rarely recognized at first sight. Our patient, the 12-year-old firstborn son of non-consanguineous parents presented with generalized mottled pigmentation starting from lower extremities. His siblings suffered from similar condition. The clue for diagnosis is the amyloid deposition in the papillary dermis. The etiology of ACD is still unknown, but genetic factors and ultraviolet radiation are implicated. It is proposed that disturbance of keratinocyte repair following ultraviolet radiation results in amyloid deposition. The treatment remains a challenge. Oral acitretin treatment, thought to repair keratinization defect, gave a slight improvement in our case. Our is the first case of ACD reported in Indonesia. PMID:25386328

Hermawan, Melyawati; Rihatmadja, Rahadi; Sirait, Sondang Pandjaitan

2014-01-01

215

Family History  

MedlinePLUS

... Complications Post Treatment and Outcome GTranslate Understanding : Family History Familial intracranial aneurysms are generally defined as the ... patients with an Intracranial Aneurysm (IA) have a history of smoking at some time in their life. ...

216

Family History  

MedlinePLUS

... Home CDC 24/7: Saving Lives. Protecting People.™ Genomics All CDC Topics Search The CDC Note: Javascript ... visit this page: About CDC.gov . Public Health Genomics Genomics Family Health History Share Compartir Family History ...

217

Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease.  

PubMed

We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A>C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malin's ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population. PMID:19322595

Traoré, M; Landouré, G; Motley, W; Sangaré, M; Meilleur, K; Coulibaly, S; Traoré, S; Niaré, B; Mochel, F; La Pean, A; Vortmeyer, A; Mani, H; Fischbeck, K H

2009-10-01

218

Rural Families.  

ERIC Educational Resources Information Center

This "special focus" journal issue consists of 13 individual articles on the theme of rural family programs relating to school, health services, church, and other institutions. It includes: (1) "Towards a Rural Family Policy" (Judith K. Chynoweth and Michael D. Campbell); (2) "Montana: Council for Families Collaborates for Prevention (Jean…

Goetz, Kathy, Ed.

1992-01-01

219

A new locus (SPG47) maps to 1p13.2-1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum.  

PubMed

The hereditary spastic paraplegias (HSP) are a heterogeneous group of genetic neurodegenerative disorders in which the main feature is progressive spasticity of the lower limbs due to pyramidal tract dysfunction. Clinically HSP are divided into two forms: a pure form that presents with progressive lower limb spasticity and weakness, sensory signs and bladder dysfunction, and a complicated form, associated with more extensive neurological and extra neurological signs as well as pathological findings on brain imaging. The clinical variability observed in HSP is supported by the large underlying genetic heterogeneity. Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a frequent subtype of complicated HSP clinically characterized by a slowly progressive spastic paraparesis with cognitive impairment and thin corpus callosum (TCC). SPG11, the most frequent gene associated with HSP-TCC, encodes spatacsin, a protein of unknown function. We describe two siblings from an Arabic consanguineous family with slowly progressive spastic paraparesis, mental retardation, seizures, thin corpus callosum and periventricular white matter abnormalities. Homozygosity mapping identified a novel single candidate region of 7.3 Mb on chromosome 1p13.2-1p12. The finding of a new locus for AR-HSP-TCC further demonstrates the extensive genetic heterogeneity of this condition. PMID:21440262

Blumkin, Lubov; Lerman-Sagie, Tally; Lev, Dorit; Yosovich, Keren; Leshinsky-Silver, Esther

2011-06-15

220

Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Effects of mutant gene dosage on phenotype.  

PubMed Central

Neonatal severe hyperparathyroidism is a rare life-threatening disorder characterized by very high serum calcium concentrations (> 15 mg/dl). Many cases have occurred in families with familial hypocalciuric hypercalcemia, a benign condition transmitted as a dominant trait. Among several hypothesized relationships between the two syndromes is the suggestion that neonatal severe hyperparathyroidism is the homozygous form of familial hypocalciuric hypercalcemia. To test this hypothesis, we refined the map location of the gene responsible for familial hypocalciuric hypercalcemia on chromosome 3q. Analyses in 11 families defined marker loci closely linked to the gene responsible for familial hypocalciuric hypercalcemia. These loci were then analyzed in four families with parental consanguinity and offspring with neonatal severe hyperparathyroidism. Each individual who was homozygous for loci that are closely linked to the gene responsible for familial hypocalciuric hypercalcemia had neonatal severe hyperparathyroidism. The calculated odds of linkage between these disorders of > 350,000:1 (lod score = 5.56). We conclude that dosage of the gene defect accounts for these widely disparate clinical phenotypes; a single defective allele causes familial hypocalciuric hypercalcemia, while two defective alleles causes neonatal severe hyperparathyroidism. PMID:8132750

Pollak, M R; Chou, Y H; Marx, S J; Steinmann, B; Cole, D E; Brandi, M L; Papapoulos, S E; Menko, F H; Hendy, G N; Brown, E M

1994-01-01

221

Family Interactions in Adoptive Compared to Nonadoptive Families  

PubMed Central

Despite the large and growing numbers of adoptive families, little research describes interactions in families with adopted adolescents. Yet, adopted adolescents’ increased risk for adjustment problems, combined with the association between family interactions and adolescent adjustment in nonadoptive families, raises questions about differences in adoptive and nonadoptive family interactions. We compared observed and self-reported family interactions between 284 adoptive and 208 nonadoptive families and within 123 families with 1 adopted and 1 nonadopted adolescent. Adolescents averaged 14.9 years of age. Comparisons were made using analysis of variance incorporating hierarchical linear methods in SAS PROC MIXED to control family-related correlations in the data. Parents and children reported more conflict in adoptive families when compared with nonadoptive families. Families with 1 adopted and 1 nonadopted adolescent reported more conflict between parents and adopted adolescents. Observed parental behavior was similar across adoptive and nonadoptive children although adopted adolescents were less warm and, in families with 2 adopted children, more conflictual than nonadopted adolescents. These findings suggest a need for further investigation of the association between family interactions and adopted adolescent problem behavior. PMID:19203160

Rueter, Martha A.; Keyes, Margaret A.; Iacono, William G.; McGue, Matt

2009-01-01

222

Identification of an extensive gene cluster among a family of PPOs in Trifolium pratense L. (red clover) using a large insert BAC library  

PubMed Central

Background Polyphenol oxidase (PPO) activity in plants is a trait with potential economic, agricultural and environmental impact. In relation to the food industry, PPO-induced browning causes unacceptable discolouration in fruit and vegetables: from an agriculture perspective, PPO can protect plants against pathogens and environmental stress, improve ruminant growth by increasing nitrogen absorption and decreasing nitrogen loss to the environment through the animal's urine. The high PPO legume, red clover, has a significant economic and environmental role in sustaining low-input organic and conventional farms. Molecular markers for a range of important agricultural traits are being developed for red clover and improved knowledge of PPO genes and their structure will facilitate molecular breeding. Results A bacterial artificial chromosome (BAC) library comprising 26,016 BAC clones with an average 135 Kb insert size, was constructed from Trifolium pratense L. (red clover), a diploid legume with a haploid genome size of 440–637 Mb. Library coverage of 6–8 genome equivalents ensured good representation of genes: the library was screened for polyphenol oxidase (PPO) genes. Two single copy PPO genes, PPO4 and PPO5, were identified to add to a family of three, previously reported, paralogous genes (PPO1–PPO3). Multiple PPO1 copies were identified and characterised revealing a subfamily comprising three variants PPO1/2, PPO1/4 and PPO1/5. Six PPO genes clustered within the genome: four separate BAC clones could be assembled onto a predicted 190–510 Kb single BAC contig. Conclusion A PPO gene family in red clover resides as a cluster of at least 6 genes. Three of these genes have high homology, suggesting a more recent evolutionary event. This PPO cluster covers a longer region of the genome than clusters detected in rice or previously reported in tomato. Full-length coding sequences from PPO4, PPO5, PPO1/5 and PPO1/4 will facilitate functional studies and provide genetic markers for plant breeding. PMID:19619287

2009-01-01

223

What makes a family reliable?  

NASA Technical Reports Server (NTRS)

Asteroid families are clusters of asteroids in proper element space which are thought to be fragments from former collisions. Studies of families promise to improve understanding of large collision events and a large event can open up the interior of a former parent body to view. While a variety of searches for families have found the same heavily populated families, and some searches have found the same families of lower population, there is much apparent disagreement between proposed families of lower population of different investigations. Indicators of reliability, factors compromising reliability, an illustration of the influence of different data samples, and a discussion of how several investigations perceived families in the same region of proper element space are given.

Williams, James G.

1992-01-01

224

Familial glomerulonephritis.  

PubMed

Between 1970 and 1984, the diagnosis of glomerulonephritis was made in 860 patients on the basis of a nephritic sediment and/or renal biopsy; of these patients, 86 (10%) had at least one first-degree relative with glomerulonephritis. These patients originated from 45 families and 1674 family members were screened; 172 had glomerulonephritis, of whom 101 could be classified. The diagnostic breakdown of the 101 patients showed that 50.5% had classical Alport's syndrome; 21.8% had atypical forms; 17.8% had familial IgA glomerulonephritis; 1.9% had focal segmental glomerulosclerosis with Wolff-Parkinson-White syndrome; and 7.9% had benign familial haematuria. The proportion of patients with glomerulonephritis who had familial disease was higher than expected. The family history is an important point to consider in the examination of patients with glomerulonephritis. PMID:3153310

Rambausek, M; Hartz, G; Waldherr, R; Andrassy, K; Ritz, E

1987-07-01

225

A comprehensive catalog of human KRAB-associated zinc finger genes: Insights into the evolutionary history of a large family of transcriptional repressors  

PubMed Central

Krüppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotes. KRAB-ZNF proteins, in which a potent repressor domain is attached to a tandem array of DNA-binding zinc-finger motifs, are specific to tetrapod vertebrates and represent the largest class of ZNF proteins in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the genome sequence for key motifs and then constructed and manually curated gene models incorporating those sequences. The resulting gene catalog contains 423 KRAB-ZNF protein-coding loci, yielding alternative transcripts that altogether predict at least 742 structurally distinct proteins. Active rounds of segmental duplication, involving single genes or larger regions and including both tandem and distributed duplication events, have driven the expansion of this mammalian gene family. Comparisons between the human genes and ZNF loci mined from the draft mouse, dog, and chimpanzee genomes not only identified 103 KRAB-ZNF genes that are conserved in mammals but also highlighted a substantial level of lineage-specific change; at least 136 KRAB-ZNF coding genes are primate specific, including many recent duplicates. KRAB-ZNF genes are widely expressed and clustered genes are typically not coregulated, indicating that paralogs have evolved to fill roles in many different biological processes. To facilitate further study, we have developed a Web-based public resource with access to gene models, sequences, and other data, including visualization tools to provide genomic context and interaction with other public data sets. PMID:16606702

Huntley, Stuart; Baggott, Daniel M.; Hamilton, Aaron T.; Tran-Gyamfi, Mary; Yang, Shan; Kim, Joomyeong; Gordon, Laurie; Branscomb, Elbert; Stubbs, Lisa

2006-01-01

226

Sugar beet contains a large CONSTANS-LIKE gene family including a CO homologue that is independent of the early-bolting (B) gene locus  

PubMed Central

Floral transition in the obligate long-day (LD) plant sugar beet (Beta vulgaris ssp. vulgaris) is tightly linked to the B gene, a dominant early-bolting quantitative trait locus, the expression of which is positively regulated by LD photoperiod. Thus, photoperiod regulators like CONSTANS (CO) and CONSTANS-LIKE (COL) genes identified in many LD and short-day (SD)-responsive plants have long been considered constituents and/or candidates for the B gene. Until now, the photoperiod response pathway of sugar beet (a Caryophyllid), diverged from the Rosids and Asterids has not been identified. Here, evidence supporting the existence of a COL gene family is provided and the presence of Group I, II, and III COL genes in sugar beet, as characterized by different zinc-finger (B-box) and CCT (CO, CO-like, TOC) domains is demonstrated. BvCOL1 is identified as a close-homologue of Group 1a (AtCO, AtCOL1, AtCOL2) COL genes, hence a good candidate for flowering time control and it is shown that it maps to chromosome II but distant from the B gene locus. The late-flowering phenotype of A. thaliana co-2 mutants was rescued by over-expression of BvCOL1 thereby suggesting functional equivalence with AtCO, and it is shown that BvCOL1 interacts appropriately with the endogenous downstream genes, AtFT and AtSOC1 in the transgenic plants. Curiously, BvCOL1 has a dawn-phased diurnal pattern of transcription, mimicking that of AtCOL1 and AtCOL2 while contrasting with AtCO. Taken together, these data suggest that BvCOL1 plays an important role in the photoperiod response of sugar beet. PMID:18495636

Chia, T. Y. P.; Müller, A.; Jung, C.; Mutasa-Göttgens, E. S.

2008-01-01

227

RNA Interference Suppression of Genes in Glycosyl Transferase Families 43 and 47 in Wheat Starchy Endosperm Causes Large Decreases in Arabinoxylan Content1[C][W][OPEN  

PubMed Central

The cell walls of wheat (Triticum aestivum) starchy endosperm are dominated by arabinoxylan (AX), accounting for 65% to 70% of the polysaccharide content. Genes within two glycosyl transferase (GT) families, GT43 (IRREGULAR XYLEM9 [IRX9] and IRX14) and GT47 (IRX10), have previously been shown to be involved in the synthesis of the xylan backbone in Arabidopsis, and close homologs of these have been implicated in the synthesis of xylan in other species. Here, homologs of IRX10 TaGT47_2 and IRX9 TaGT43_2, which are highly expressed in wheat starchy endosperm cells, were suppressed by RNA interference (RNAi) constructs driven by a starchy endosperm-specific promoter. The total amount of AX was decreased by 40% to 50% and the degree of arabinosylation was increased by 25% to 30% in transgenic lines carrying either of the transgenes. The cell walls of starchy endosperm in sections of grain from TaGT43_2 and TaGT47_2 RNAi transgenics showed decreased immunolabeling for xylan and arabinoxylan epitopes and approximately 50% decreased cell wall thickness compared with controls. The proportion of AX that was water soluble was not significantly affected, but average AX polymer chain length was decreased in both TaGT43_2 and TaGT47_2 RNAi transgenics. However, the long AX chains seen in controls were absent in TaGT43_2 RNAi transgenics but still present in TaGT47_2 RNAi transgenics. The results support an emerging picture of IRX9-like and IRX10-like proteins acting as key components in the xylan synthesis machinery in both dicots and grasses. Since AX is the main component of dietary fiber in wheat foods, the TaGT43_2 and TaGT47_2 genes are of major importance to human nutrition. PMID:23878080

Lovegrove, Alison; Wilkinson, Mark D.; Freeman, Jackie; Pellny, Till K.; Tosi, Paola; Saulnier, Luc; Shewry, Peter R.; Mitchell, Rowan A.C.

2013-01-01

228

Family Potyviridae  

Technology Transfer Automated Retrieval System (TEKTRAN)

The International Committee on the Taxonomy of Viruses potyvirus study group has revised the description of the family Potyviridae for inclusion in the ICTV 9th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of viral sp...

229

FAMILY GEMINIVIRIDAE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The International Committee on the Taxonomy of Viruses geminivirus study group has revised the description of the family Geminiviridae for inclusion in the ICTV 8th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of vi...

230

Family Workshops  

ERIC Educational Resources Information Center

A Family Workshop is an informal, multidisciplined educational program for adults and children, organized by a team of teachers. This article discusses the Lavender Hill Family Workshop, one of many, which attempts to provide education in various subject areas for adults and for children while also integrating both objectives in order to educate…

Bennett, Dave; Rees-Jones, Tanny

1978-01-01

231

Family Life.  

ERIC Educational Resources Information Center

Focuses on various aspects of mammal family life ranging from ways different species are born to how different mammals are raised. Learning activities include making butter from cream, creating birth announcements for mammals, and playing a password game on family life. (ML)

Naturescope, 1986

1986-01-01

232

FAMILY POTYVIRIDAE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The International Committee on the Taxonomy of Viruses potyvirus study group has revised the description of the family Geminiviridae for inclusion in the ICTV 8th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of vira...

233

Familial glomerulonephritis  

Microsoft Academic Search

Between 1970 and 1984, the diagnosis of glomerulonephritis was made in 860 patients on the basis of a nephritic sediment and\\/or renal biopsy; of these patients, 86 (10%) had at least one first-degree relative with glomerulonephritis. These patients originated from 45 families and 1674 family members were screened; 172 had glomerulonephritis, of whom 101 could be classified. The diagnostic breakdown

Michael Rambausek; Georg Hartz; Rüdiger Waldherr; Konrad Andrassy; Eberhard Ritz

1987-01-01

234

Premutation for the Martin-Bell syndrome analyzed in a large Sardinian family: III. Molecular analysis with the StB12.3 probe  

SciTech Connect

This report complements a series of clinical, cytogenetical, and psychological studies previously reported on a large Sardinian pedigree segregating for premutations and full mutations associated with the Martin-Bell syndrome (MBS). Using the StB12.3 probe, we report now the molecular classification of all of the critical members of the pedigree. These molecular findings are evaluated against the variable phenotypic manifestations of the disease in the course of a six-generation segregation of an MBS premutation allegedly present in a common female progenitor of 14 MBS male patients and 9 female MBS heterozygotes seen in the last two generations. The nature and stepwise progression of MBS-premutations toward the fully manifested Martin-Bell syndrome and the possibility of reverse mutational events toward the normal allele are discussed with respect to the application of the presently available diagnostic tools in genetic counseling. 12 refs., 1 fig.

Grasso, M.; Perroni, L.; Dagna-Bricarelli, F. [Centro di Genetica Umana, Genova (Italy)] [and others] [Centro di Genetica Umana, Genova (Italy); and others

1996-08-09

235

Family Theory and Family Health Research  

PubMed Central

Different family theories can be applied to different aspects of how families experience health and illness. The family health and illness cycle describes the phases of a family's experience, beginning with health promotion and risk reduction, then family vulnerability and disease onset or relapse, family illness appraisal, family acute response, and finally family adaptation to illness and recovery. For each phase, specific family theories that are most appropriate for guiding family and health research are discussed. PMID:21229056

Doherty, William J.

1991-01-01

236

Challenges and solutions for gene identification in the presence of familial locus heterogeneity.  

PubMed

Next-generation sequencing (NGS) of exomes and genomes has accelerated the identification of genes involved in Mendelian phenotypes. However, many NGS studies fall short of identifying causal variants, with estimates for success rates as low as 25% for uncovering the pathological variant underlying disease etiology. An important reason for such failures is familial locus heterogeneity, where within a single pedigree causal variants in two or more genes underlie Mendelian trait etiology. As examples of intra- and inter-sibship familial locus heterogeneity, we present 10 consanguineous Pakistani families segregating hearing impairment due to homozygous variants in two different hearing impairment genes and a European-American pedigree in which hearing impairment is caused by four variants in three different genes. We have identified 41 additional pedigrees with syndromic and nonsyndromic hearing impairment for which a single previously reported hearing impairment gene has been identified but only segregates with the phenotype in a subset of affected pedigree members. We estimate that locus heterogeneity occurs in 15.3% (95% confidence interval: 11.9%, 19.9%) of the families in our collection. We demonstrate novel approaches to apply linkage analysis and homozygosity mapping (for autosomal recessive consanguineous pedigrees), which can be used to detect locus heterogeneity using either NGS or SNP array data. Results from linkage analysis and homozygosity mapping can also be used to group sibships or individuals most likely to be segregating the same causal variants and thereby increase the success rate of gene identification.European Journal of Human Genetics advance online publication, 10 December 2014; doi:10.1038/ejhg.2014.266. PMID:25491636

Rehman, Atteeq U; Santos-Cortez, Regie Lyn P; Drummond, Meghan C; Shahzad, Mohsin; Lee, Kwanghyuk; Morell, Robert J; Ansar, Muhammad; Jan, Abid; Wang, Xin; Aziz, Abdul; Riazuddin, Saima; Smith, Joshua D; Wang, Gao T; Ahmed, Zubair M; Gul, Khitab; Shearer, A Eliot; Smith, Richard J H; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Hinnant, John; Khan, Shaheen N; Fisher, Rachel A; Ahmad, Wasim; Friderici, Karen H; Riazuddin, Sheikh; Friedman, Thomas B; Wilch, Ellen S; Leal, Suzanne M

2014-12-10

237

[Family ideology].  

PubMed

This paper treats the definition of the concept of family ideology linking it to that of social ideology. In both cases the ideology is seen as patterns of messages that obey certain semantic rules. Within the family context, it is considered that the conditions of production of the ideology are, concerning the profound structures, the unconscious oedipus conflict and kindred system that determines the family organization. Concerning the surface structures, the myths and beliefs that appear in each group as an answer to the need of accounting for the conflicts inherent to the family structure. The family ideology guides the subjects to places predetermined by the oedipus conflicts, "semanticizes" the conflicts and tends to dissimulate the conditions of production through the illusion that the subject is the producer. To analyze the family ideology, the following items must be taken into account: 1) Which are the semantic lines that are privileged in the couple and parent-children relationships. 2) The relations between the semantic lines established by the articulation rules prescribed by the cultural system. 3) The elementary forms of the ideological universe (the "actantial" model applied to family relationships). These three aspects articulate between themselves through transformation rules. PMID:7136827

Kornblit, A

1982-06-01

238

Unusual families.  

PubMed

The introduction of assisted reproduction has led to unusual forms of procreation. This article describes the social consequences of lesbian motherhood and of families headed by single heterosexual mothers. PMID:15819999

Golombok, Susan

2005-03-01

239

Family Money  

NSDL National Science Digital Library

Family Money is an investment center from Better Homes and Gardens Online. A wide variety of columns advise readers on home finance issues, and additional site tools include savings, loan, and car lease calculators for financial planning purposes.

240

Fact Families  

NSDL National Science Digital Library

In this lesson, the relationship of addition to subtraction is explored with books and with connecting cubes. Students search for related addition and subtraction facts for a given number using a virtual or actual calculator to find differences. They also investigate fact families when one addend is 0 as well as when the addends are the same. Students will: find missing addends, review the additive identity, generate fact families given two addends or given one addend and the sum.

Illuminations

2012-03-31

241

Jobcode Jobcode Descr Family Job Family Descr Ben Family  

E-print Network

Jobcode Jobcode Descr Job Family Job Family Descr Ben Family Sal Admin Plan Sal Grade Reg Temp FLSA Prof/Admin 93 33 HJC T N N No IPEDS-S Reporting 999 BWC N 010620 NUCLEAR MED TECH (TEMP) 33 Temporary T N N No IPEDS-S Reporting 000 BWC N #12;Jobcode Jobcode Descr Job Family Job Family Descr Ben Family

Awtar, Shorya

242

The Pfam protein families database  

Microsoft Academic Search

Pfam is a large collection of protein families and domains. Over the past 2 years the number of families in Pfam has doubled and now stands at 6190 (version 10.0). Methodology improvements for searching the Pfam collection locally as well as via the web are described. Other recent innovations include modelling of discontinuous domains allow- ing Pfam domain definitions to

Alex Bateman; Lachlan James M. Coin; Richard Durbin; Robert D. Finn; Volker Hollich; Sam Griffiths-jones; Ajay Khanna; Mhairi Marshall; Simon Moxon; Erik L. L. Sonnhammer; David J. Studholme; Corin Yeats; Sean R. Eddy

2004-01-01

243

Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations  

PubMed Central

Purpose Autosomal recessive retinitis pigmentosa (arRP) is a genetically heterogeneous disease resulting in progressive loss of photoreceptors that leads to blindness. To date, 36 genes are known to cause arRP, rendering the molecular diagnosis a challenge. The aim of this study was to use homozygosity mapping to identify the causative mutation in a series of inbred families with arRP. Methods arRP patients underwent standard ophthalmic examination, Goldman perimetry, fundus examination, retinal OCT, autofluorescence measurement, and full-field electroretinogram. Fifteen consanguineous families with arRP excluded for USH2A and EYS were genotyped on 250 K SNP arrays. Homozygous regions were listed, and known genes within these regions were PCR sequenced. Familial segregation and mutation analyzes were performed. Results We found ten mutations, seven of which were novel mutations in eight known genes, including RP1, IMPG2, NR2E3, PDE6A, PDE6B, RLBP1, CNGB1, and C2ORF71, in ten out of 15 families. The patients carrying RP1, C2ORF71, and IMPG2 mutations presented with severe RP, while those with PDE6A, PDE6B, and CNGB1 mutations were less severely affected. The five families without mutations in known genes could be a source of identification of novel genes. Conclusions Homozygosity mapping combined with systematic screening of known genes results in a positive molecular diagnosis in 66.7% of families. PMID:24339724

Marzouka, Nour al Dain; Hebrard, Maxime; Manes, Gaël; Sénéchal, Audrey; Meunier, Isabelle; Hamel, Christian P.

2013-01-01

244

Roles within the Family  

MedlinePLUS

... Us My Cart Healthy Children > Family Life > Family Dynamics > Roles Within the Family Family Life Listen Roles Within the Family Article Body Families are not democracies. Each family has its own ways of deciding who has the power and authority within the family unit, and which ...

245

Family Hypnotherapy.  

ERIC Educational Resources Information Center

A therapeutic model to help families activate experiential and right hemispheric functioning through hypnosis is presented in detail, together with a clinical illustration. Different situations in which this model is effective are mentioned and one such set of circumstances is described. (Author)

Araoz, Daniel L.; Negley-Parker, Esther

1985-01-01

246

FAMILY TYMOVIRIDAE  

Technology Transfer Automated Retrieval System (TEKTRAN)

This article provides a brief review of the taxonomic structure, virion properties, genome organization and replication strategy, antigenic properties, and biological properties of viruses in the family Tymoviridae. Criteria for demarcation of genus and species are provided. A brief review of each...

247

Family Violence.  

ERIC Educational Resources Information Center

This quarterly publication, issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), contains articles dealing with family violence and alcohol abuse, children of alcoholic parents, training programs for counselors, and confidentiality of client records. The three articles on alcohol abuse suggest that: (1) there is a clear…

Sorgen, Carol, Ed.

1979-01-01

248

Family Caregivers.  

ERIC Educational Resources Information Center

This document contains a brief bibliography of peer-reviewed literature, with abstracts, on family caregiving. It is one of 12 bibliographies on aging prepared by the National Agricultural Library for its "Pathfinders" series of publications. Topics covered by the other 11 bibliographies include aging parents, adult children, dementia and…

Frazier, Billie H.

249

A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor apraxia.  

PubMed

Autosomal recessive ataxias are heterogeneous group of disorders characterized by cerebellar atrophy and peripheral sensorimotor neuropathy. Molecular characterization of this group of disorders identified a number of genes contributing to these overlapping phenotypes. Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive form of ataxia caused by mutations in the SETX gene. We report on a consanguineous family with autosomal recessive inheritance and clinical characteristics of AOA2, and no mutations in the SETX gene. We mapped the AOA locus in this family to chromosome 17p12-p13. Sequencing of all genes in the refined region identified a homozygous missense mutation in PIK3R5 that was absent in 477 normal controls. Our characterization of the PIK3R5 protein and findings suggest that it may play a role in the development of the cerebellum and vermis. PMID:22065524

Al Tassan, Nada; Khalil, Dania; Shinwari, Jameela; Al Sharif, Latifa; Bavi, Prashant; Abduljaleel, Zainularifeen; Abu Dhaim, Nada; Magrashi, Amna; Bobis, Steve; Ahmed, Hala; Alahmed, Samaher; Bohlega, Saeed

2012-02-01

250

Family Child Care Licensing Study, 2003.  

ERIC Educational Resources Information Center

This report presents the findings of the 2003 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2002 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Hollestelle, Kay; Koch, Pauline D.

251

Family Child Care Licensing Study, 2002.  

ERIC Educational Resources Information Center

This report presents the findings of the 2002 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2001 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Children's Foundation, Washington, DC.

252

The Family Child Care Licensing Study, 1999.  

ERIC Educational Resources Information Center

This report presents the findings of the 1999 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1998 study. Data on small family child care homes and group or large family child care homes are organized in 22 categories: (1) number of regulated homes; (2)…

Children's Foundation, Washington, DC.

253

Family Child Care Licensing Study, 2001.  

ERIC Educational Resources Information Center

This report presents the findings of the 2001 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2000 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Children's Foundation, Washington, DC.

254

Family Child Care Licensing Study, 2000.  

ERIC Educational Resources Information Center

This report presents the findings of the 2000 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1999 study. Data on small family child care homes and group or large family child care homes are organized in 23 categories: (1) number of regulated homes; (2)…

Kelly, Nia, Comp.

255

FAMILIES OF ALGEBRAIC VARIETIES AND INVARIANT CYCLES  

Microsoft Academic Search

This paper studies monodromy-invariant cycles in the cohomology of fibers of a family of algebraic varieties. It is shown that the localization of invariant cycles in a neighborhood of a degeneration of the family is a morphism of Hodge structures. An application of this result is the geometric analogue of the Mumford-Tate conjecture for families with strong degenerations. A large

G A Mustafin

1986-01-01

256

A Lebanese family with autosomal recessive oculo-auriculo-vertebral (OAV) spectrum and review of the literature: is OAV a genetically heterogeneous disorder?  

PubMed Central

Oculo-auriculo-vertebral (OAV) spectrum summarizes a continuum of ocular, auricular, and vertebral anomalies. Goldenhar syndrome is a variant of this spectrum and is characterized by pre-auricular skin tags, microtia, facial asymmetry, ocular abnormalities, and vertebral anomalies of different sizes and shapes. Most cases are thought to be sporadic. However, a few families were reported to have an autosomal recessive inheritance and other families’ presentation of the syndrome strongly supported an autosomal dominant inheritance. We report OAV in a female infant presenting with tracheomalacia, diaphragmatic hernia, encephalomeningocele, sacral neural tube defect, and cardiac defect and her brother having no more than dysmorphic features. The mode of inheritance in this family supports an autosomal recessive inheritance where the transmission was from normal first-degree consanguineous parents to one of the sons and to the daughter. This report further broadens the clinical presentation and symptoms of OAV and supports the hypothesis advancing OAV as a genetically heterogeneous disorder. PMID:23776370

Farra, Chantal; Yunis, Khaled; Yazbeck, Nadine; Majdalani, Marianne; Charafeddine, Lama; Wakim, Rima; Awwad, Johnny

2011-01-01

257

Progressive dystonia with optic atrophy in a Jewish-Iraqi family.  

PubMed

The combination of progressive dystonia and optic atrophy is extremely rare and its morphological, metabolic and genetic basis is unknown. In a family of 9 children (8 males) born to consanguineous Israeli-Jewish-Iraqi parents, we identified four brothers who developed the syndrome at the end of the first decade. Patients had hemi or bilateral dystonia associated with striatal, mainly putaminal, atrophy on CT and MRI, various degrees of optic atrophy, minimal corticospinal tract involvement, normal intelligence and no peripheral nervous system or systemic abnormalities. No causative metabolic defect was identified. None of the several known mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy (LHON) or with LHON with dystonia were detected. Likewise, linkage to the idiopathic torsion dystonia region on chromosome 9q34 was excluded. It is suggested that this in our patients might be due to a yet unidentified genomic, autosomal recessive mutation. PMID:9335011

Korn-Lubetzki, I; Blumenfeld, A; Gomori, J M; Soffer, D; Steiner, I

1997-10-01

258

Familial Hypercholesterolemia  

PubMed Central

Background Familial hypercholesterolemia (FH) is an autosomal dominant-inherited genetic disorder that leads to elevated blood cholesterol levels. FH may present as severely elevated total cholesterol and low density lipoprotein (LDL) cholesterol levels or as premature coronary heart disease (CHD). Methods This review presents information on the disease and on the effects of drug treatment and lifestyle changes. Results Routine lipid testing should identify most patients with FH. Once an index case is identified, testing should be offered to family members. Early diagnosis and aggressive treatment with therapeutic lifestyle changes and statins can prevent premature CHD and other atherosclerotic sequelae in patients with FH. Conclusion Emerging therapies such as LDL apheresis and novel therapeutic agents may be useful in patients with homozygous FH or treatment-resistant FH. Liver transplantation is the only effective therapy for severe cases of homozygous FH. PMID:25598733

Pejic, Rade N.

2014-01-01

259

Family Psychology and Family Therapy in Japan.  

ERIC Educational Resources Information Center

Reviews the development of family psychology and family therapy in Japan, tracing the origins of these movements, explaining how these fields were activated by the problem of school refusal, and describing an approach to family therapy that has been developed to work with families confronting this problem, as well as preventive programs of family

Kameguchi, Kenji; Murphy-Shigematsu, Stephen

2001-01-01

260

Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene  

PubMed Central

AIM To make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology. METHODS A five-generation Han Chinese family diagnosed as non-syndromic X-linked recessive RP (XLRP) was recruited, including four affected males, four obligate female carriers and eleven unaffected family members. Capture-NGS was performed using a custom designed capture panel covers 163 known retinal disease genes including 47 RP genes, followed by the validation of detected mutation using Sanger sequencing in all recruited family members. RESULTS Capture-NGS in one affected 47-year-old male reveals a novel mutation, c.2417_2418insG:p.E806fs, in exon ORF15 of RP GTPase regulator (RPGR) gene results in a frameshift change that results in a premature stop codon and a truncated protein product. The mutation was further validated in three of four affected males and two of four female carriers but not in the other unaffected family members. CONCLUSION We have identified a novel mutation, c.2417_2418insG:p.E806fs, in a Han Chinese family with XLRP. Our findings expand the mutation spectrum of RPGR and the phenotypic spectrum of XLRP in Han Chinese families, and confirms Capture-NGS could be an effective and economic approach for the comprehensive molecular diagnosis of RP. PMID:25349787

Hu, Fang; Zeng, Xiang-Yun; Liu, Lin-Lin; Luo, Yao-Ling; Jiang, Yi-Ping; Wang, Hui; Xie, Jing; Hu, Cheng-Quan; Gan, Lin; Huang, Liang

2014-01-01

261

Large vestibular aqueduct syndrome.  

PubMed

Large Vestibular Aqueduct Syndrome is a congenital malformation of the temporal bone characterised by early onset of sensorineural hearing loss and vestibular disturbance. Familial large vestibular aqueduct syndrome suggests autosomal recessive or X-linked inheritance and accounts for non-syndromic sensorineural hearing loss in these patients. PMID:16570713

Dipak, S; Prepageran, N; Sazila, A S; Rahmat, O; Raman, R

2005-10-01

262

The Pfam Protein Families Database  

Microsoft Academic Search

Pfam is a large collection of protein multiple sequence alignments and profile hidden Markov models. Pfam is available on the WWW in the UK at http:\\/\\/www.sanger.ac.uk\\/Software\\/Pfam\\/ , in Sweden at http:\\/\\/www.cgr.ki.se\\/Pfam\\/ and in the US at http:\\/\\/ pfam.wustl.edu\\/ . The latest version (4.3) of Pfam contains 1815 families. These Pfam families match 63% of proteins in SWISS-PROT 37 and TrEMBL

Alex Bateman; Ewan Birney; Richard Durbin; Sean R. Eddy; Kevin L. Howe; Erik L. L. Sonnhammer

2000-01-01

263

The putative chemoreceptor families of  

Microsoft Academic Search

Chemoreception of environmental stimuli is a major sensory system in small soil nematodes like C. elegans. As in other animals, chemoreception is mediated in C. elegans by members of the seven-transmembrane G-protein-coupled receptor class (7TM GPCRs). We summarize the many large putative chemoreceptor gene families, including the str family (which includes odr-10, the only receptor with an identified ligand), and

Hugh M. Robertso; James H. Thomas

264

A novel family of insect-selective peptide neurotoxins targeting insect large-conductance calcium-activated K+ channels isolated from the venom of the theraphosid spider Eucratoscelus constrictus.  

PubMed

Spider venoms are actively being investigated as sources of novel insecticidal agents for biopesticide engineering. After screening 37 theraphosid spider venoms, a family of three new "short-loop" inhibitory cystine knot insecticidal toxins (?-TRTX-Ec2a, ?-TRTX-Ec2b, and ?-TRTX-Ec2c) were isolated and characterized from the venom of the African tarantula Eucratoscelus constrictus. Whole-cell patch-clamp recordings from cockroach dorsal unpaired median neurons revealed that, despite significant sequence homology with other theraphosid toxins, these 29-residue peptides lacked activity on insect voltage-activated sodium and calcium channels. It is noteworthy that ?-TRTX-Ec2 toxins were all found to be high-affinity blockers of insect large-conductance calcium-activated K(+) (BK(Ca)) channel currents with IC(50) values of 3 to 25 nM. In addition, ?-TRTX-Ec2a caused the inhibition of insect delayed-rectifier K(+) currents, but only at significantly higher concentrations. ?-TRTX-Ec2a and ?-TRTX-Ec2b demonstrated insect-selective effects, whereas the homologous ?-TRTX-Ec2c also resulted in neurotoxic signs in mice when injected intracerebroventricularly. Unlike other theraphosid toxins, ?-TRTX-Ec2 toxins induce a voltage-independent channel block, and therefore, we propose that these toxins interact with the turret and/or loop region of the external entrance to the channel and do not project deeply into the pore of the channel. Furthermore, ?-TRTX-Ec2a and ?-TRTX-Ec2b differ from other theraphotoxins at the C terminus and positions 5 to 6, suggesting that these regions of the peptide contribute to the phyla selectivity and are involved in targeting BK(Ca) channels. This study therefore establishes these toxins as tools for studying the role of BK(Ca) channels in insects and lead compounds for the development of novel insecticides. PMID:21447641

Windley, Monique J; Escoubas, Pierre; Valenzuela, Stella M; Nicholson, Graham M

2011-07-01

265

Brief Psychotherapy in Family Practice  

PubMed Central

A large number of patients with psychosocial or psychiatric disorders present to family physicians, and the family physician needs a model of psychotherapy with which to cope with their problems. A model of brief psychotherapy is presented which is time limited, goal directed and easy to learn. It consists of four facets drawn from established areas of psychotherapy: characteristics of the therapist; characteristics of the patient; Eriksonian developmental stages; and the process of therapy as described by Carkhuff. These facets fit together in a way which is useful to the family physician in managing those patient problems for which brief psychotherapy is indicated. PMID:21267176

MacDonald, Peter J.; Brown, Alan

1986-01-01

266

Reclaiming Family Privilege  

ERIC Educational Resources Information Center

The pull for family is strong, almost primeval, most likely it is evolutionary, and for those lacking the benefit of family or Family Privilege, the loss of family is painful and profoundly sad. Young people who struggle to cope without stable family connections are profoundly aware of their lack of "Family Privilege." In this article, the author…

Seita, John

2012-01-01

267

Thankful for Family and Foods! (An ABLE Teaching Unit).  

ERIC Educational Resources Information Center

The teaching unit focuses on a month (November) of primary grade learning activities which focus on being thankful for food, family, and friends. Concepts stressed throughout the unit include: We are all part of the large family of Americans; Families are made up of a variety of people and our families are usually different from each other;…

Barringer, Mary Dean; And Others

268

Religious Influences on Work-Family Trade-Offs  

ERIC Educational Resources Information Center

Despite a large body of research on the influences of religion on family life and gender ideology, few studies examined how religion affects work-family strategies. One set of strategies involves making employment or family trade-off--strategies of devoting time or attention to either work or family in a situation in which one cannot devote the…

Ammons, Samantha K.; Edgell, Penny

2007-01-01

269

Significance of the parkin and PINK1 gene in Jordanian families with incidences of young-onset and juvenile parkinsonism  

PubMed Central

Background Parkinson's disease is a progressive neurodegenerative disorder, where most cases are sporadic with a late onset. In rare incidences familial forms of early-onset parkinsonism occur, and when recessively inherited, cases are often explained by mutations in either the parkin (PARK2) or PINK1 (PARK6) gene or on exceptional occasions the DJ-1 (PARK7) or ATP13A2 (PARK9) gene. Recessively inherited deletions/duplications and point mutations in the parkin gene are the most common cause of early-onset parkinsonism known so far, but in an increasing number of studies, genetic variations in the serine/threonine kinase domain of the PINK1 gene are found to explain early-onset parkinsonism. Methods In this study all families were from a population with a high incidence of consanguinity. We investigated 11 consanguineous families comprising 17 affected with recessively inherited young-onset parkinsonism for mutations both in the parkin and PINK1 gene. Exons and flanking regions were sequenced, and segregation patterns of genetic variation were assessed in members of the respective families. An exon dosage analysis was performed for all exons in both genes. Results In the parkin gene, a three generation family was identified with an exon 4 deletion segregating with disease. Both affected were homozygous for the deletion that segregated on a haplotype that spanned the gene in a haplotype segregation analysis that was performed using additional markers. Exon dosage analysis confirmed the recessive pattern of inheritance with heterozygous deletions segregating in healthy family members. In the PINK1 gene we identified two novel putative pathogenic substitutions, P416R and S419P, located in a conserved motif of the serine/threonine kinase domain. Both substitutions segregated with disease in agreement with a recessive pattern of inheritance within respective families and both were present as homozygous in two affected each. We also discuss common polymorphisms in the two genes found to be co-segregating within families. Conclusion Our results further extend on the involvement of PINK1 mutations in recessive early-onset parkinsonism with clinical features similar to carriers of parkin mutations. PMID:19087301

Myhre, Ronny; Steinkjer, Stina; Stormyr, Alice; Nilsen, Gina L; Zayyad, Hiba Abu; Horany, Khalid; Nusier, Mohamad K; Klungland, Helge

2008-01-01

270

Psychoanalysis: a dysfunctional family?  

PubMed

The discussion opens with an account of the author's mother's bizarre family in which a strong, charismatic grandmother maintained absolute control over her large family by encouraging a neurotic dependence in them through daily reports of their complaints. Getting interested in psychoanalysis in an effort to understand the dynamics of this dysfunctional family, the author, a biographer, turned to the study of Melanie Klein, becoming entranced by her ideas. Her research also revealed how Klein had discouraged her followers from developing ideas that diverged in any way from her own. Her portrait of the pioneer analyst provoked intense indignation. A similar pattern of absolute loyalty to his person and theories was to be found in Freud's Secret Committee, formed primarily as a means of getting rid of Jung who had been showing disturbing signs of independence. When Ferenczi and Rank began to pursue independent lines of enquiry in their work, they too were though to be undermining the foundations of classical psychoanalysis. Finally, the author concludes that though there have been sorry incidents in psychoanalysis, we should be mature enough to accept both the contributions of the early pioneers and the realizations that new ideas must be permitted to evolve. PMID:9531859

Grosskurth, P

1998-01-01

271

Family and family therapy in Russia.  

PubMed

This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized. PMID:22515460

Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

2012-04-01

272

The Changing Family Structure.  

ERIC Educational Resources Information Center

This newsletter issue contains feature articles and short reports on how and why family structures are undergoing substantial change in many parts of the world. These articles include: (1) "The Changing Family Structure," a review of how families are changing and why; (2) "Peru: Families in the Andes"; (3) "Thailand: Families of the Garbage Dump";…

Bernard van Leer Foundation Newsletter, 1993

1993-01-01

273

Families with Gifted Adolescents  

ERIC Educational Resources Information Center

Studies of families with gifted adolescents have revealed conflicting results. Adolescents, mothers, and fathers of 84 families with a gifted adolescent and of 95 families with a non-gifted adolescent evaluated their family system independently. Dependent variables were cohesion, democratic family style (adaptability), organisation, achievement…

Schilling, Susanne R.; Sparfeldt, Jorn; Rost, Detlef H.

2006-01-01

274

Family Resiliency: A Neglected Family Construct.  

ERIC Educational Resources Information Center

Examines research on the construct of resiliency and examines factors that promote resiliency in individuals and families. Implications for family counselors, societal systems, and future research are discussed. (Author/MKA)

Buckley, Matthew R.; Thorngren, Jill M.; Kleist, David M.

1997-01-01

275

The expanding family Marseilleviridae.  

PubMed

The family Marseilleviridae encompasses giant viruses that replicate in free-living Acanthamoeba amoebae. Since the discovery of the founding member Marseillevirus in 2007, 7 new marseilleviruses have been observed, including 3 from environmental freshwater, one from a dipteran, and two from symptom-free humans. Marseilleviruses have ?250-nm-large icosahedral capsids and 346-386-kb-long mosaic genomes that encode 444-497 predicted proteins. They share a small set of core genes with Mimivirus and other large and giant DNA viruses that compose a monophyletic group, first described in 2001. Comparative genomics analyses indicate that the family Marseilleviridae currently includes three lineages and a pan-genome composed of ?600 genes. Antibodies against marseilleviruses and viral DNA have been observed in a significant proportion of asymptomatic individuals and in the blood and lymph nodes of a child with adenitis; these observations suggest that these giant viruses may be blood borne and question if they may be pathogenic in humans. PMID:25104553

Aherfi, Sarah; La Scola, Bernard; Pagnier, Isabelle; Raoult, Didier; Colson, Philippe

2014-10-01

276

Genetic homogeneity in Sjoegren-Larsson syndrome: Linkage to chromosome 17p in families of different non-Swedish ethnic origins  

SciTech Connect

Sjoegren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder that is characterized by congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. Three United States families, three Egyptian families, and one Israeli Arab family were investigated for linkage of the SLS gene to a region of chromosome 17. Pairwise and multipoint linkage analysis with nine markers mapped the SLS gene to the same region of the genome as that reported in Swedish SLS pedigrees. Examination of recombinants by haplotype analysis showed that the gene lies in the region containing the markers D17S953, D17S805, D17S689, and D17S842. D17S805 is pericentromeric on 17p. Patients in two consanguineous Egyptian families were homozygous at the nine marker loci tested, and another patient from a third family was homozygous for eight of the nine, suggesting that within each of these families the region of chromosome 17 carrying the SLS gene is identical by descent. Linkage of the SLS gene to chromosome 17p in families of Arabic, mixed European, Native American, and Swedish descent provides evidence for a single SLS locus and should prove useful for diagnosis and carrier detection in worldwide cases. 25 refs., 4 figs., 1 tab.

Rogers, G.R.; Lee, M.; Compton, J.G. [and others

1995-11-01

277

Bounding CKM Mixing with a Fourth Family  

SciTech Connect

CKM mixing between third family quarks and a possible fourth family is constrained by global fits to the precision electroweak data. The dominant constraint is from nondecoupling oblique corrections rather than the vertex correction to Z {yields} {bar b}b used in previous analyses. The possibility of large mixing suggested by some recent analyses of FCNC processes is excluded, but 3-4 mixing of the same order as the Cabbibo mixing of the first two families is allowed.

Chanowitz, Michael S.

2009-04-22

278

Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246  

SciTech Connect

This report presents refined genetic mapping data for the gene causing familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation. We sampled 65 Jewish, Armenian, and Arab families and typed them for eight markers from chromosome 16p. Using a new algorithm that permits multipoint calculations for a dense map of markers in consanguineous families, we obtained a maximal LOD score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype at D16S283-D16S94-D16S246 was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Moreover, the 2.5-kb allele at D16S246 was significantly associated with FMF in Moroccan and non-Moroccan Jews but not in Armenians or Arabs. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, we analyzed the Moroccan linkage-disequilibrium data by using Luria-Delbruck formulas and simulations based on a Poisson branching process. These methods place the FMF susceptibility gene within 0.305 cM of D16S246 (2-LOD-unit range 0.02-0.64 cM). 41 refs., 3 figs., 5 tabs.

Levy, E. N.; Aksentijevich, I.; Pras, E. [National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD (United States)] [and others

1996-03-01

279

Distribution of Mycorrhizal Types among Alpine Vascular Plant Families on the Beartooth Plateau, Rocky Mountains, U.S.A., in Reference to Large-Scale Patterns in Arctic–Alpine Habitats  

Microsoft Academic Search

Mycorrhizal symbiosis is critical to plant establishment and survival, influences plant community structure and function, and could be particularly important in harsh environments such as the alpine tundra. An examination of 53 vascular plant species in 21 families from alpine areas of the Beartooth Plateau (Rocky Mountains) revealed most were mycorrhizal (68%) and four distinct types of symbioses were present.

Cathy L. Cripps; Leslie H. Eddington

2005-01-01

280

Family Capital: Implications for Interventions with Families  

ERIC Educational Resources Information Center

Social capital has been extensively discussed in the literature as building blocks that individuals and communities utilize to leverage system resources. Similarly, some families also create capital, which can enable members of the family, such as children, to successfully negotiate the outside world. Families in poverty confront serious…

Belcher, John R.; Peckuonis, Edward V.; Deforge, Bruce R.

2011-01-01

281

Transient familial hyperbilirubinemia  

MedlinePLUS

Transient familial hyperbilirubinemia is a metabolic disorder that is passed down through families. Babies with this disorder ... Transient familial hyperbilirubinemia is an inherited disorder. It occurs when the body does not properly break down ( ...

282

Managing a Family Budget  

E-print Network

- ry. Producers may rarely go back and compare their actual family living expenses against their budgeted amounts. Dean A. McCorkle, Steven L. Klose and Danny Klinefelter* Why Develop a Family Living Budget Budgeting for family expenditures...

McCorkle, Dean; Klinefelter, Danny A.

2008-09-16

283

Family Child Care Licensing Study, 1997.  

ERIC Educational Resources Information Center

This report details the findings of an annual survey of state child care regulatory agencies. The survey gathered data on both small family child care homes and group or large family child care homes in each of the 50 states, the District of Columbia, Puerto Rico and the Virgin Islands. The report's introduction lists the survey categories and…

Children's Foundation, Washington, DC.

284

Family Child Care Licensing Study, 1998.  

ERIC Educational Resources Information Center

This report details a survey of state child care regulatory agencies. Data on both small family child care homes (FCCH) and group or large family child care homes (LCCH or GCCH) are included and organized into 22 categories: (1) number of regulated homes; (2) definitions and regulatory requirements; (3) unannounced inspection procedure; (4)…

Children's Foundation, Washington, DC.

285

Characterization of familial breast cancer in Saudi Arabia  

PubMed Central

Background The contribution of genetic factors to the development of breast cancer in the admixed and consanguineous population of the western region of Saudi Arabia is thought to be significant as the disease is early onset. The current protocols of continuous clinical follow-up of relatives of such patients are costly and cause a burden on the usually over-stretched medical resources. Discovering the significant contribution of BRCA1/2 mutations to breast cancer susceptibility allowed for the design of genetic tests that allows the medical practitioner to focus the care for those who need it most. However, BRCA1/2 mutations do not account for all breast cancer susceptibility genes and there are other genetic factors, known and unknown that may play a role in the development of such disease. The advent of whole-exome sequencing is offering a unique opportunity to identify the breast cancer susceptibility genes in each family of sufferers. The polymorphisms/mutations identified will then allow for personalizing the genetic screening tests accordingly. To this end, we have performed whole-exome sequencing of seven breast cancer patients with positive family history of the disease using the Agilent SureSelect™ Whole-Exome Enrichment kit and sequencing on the SOLiD™ platform. Results We have identified several coding single nucleotide variations that were either novel or rare affecting genes controlling DNA repair in the BRCA1/2 pathway. Conclusion The disruption of DNA repair pathways is very likely to contribute to breast cancer susceptibility in the Saudi population.

2015-01-01

286

Genetic Screening for MEN1 Mutations in Families Presenting with Familial Primary Hyperparathyroidism  

Microsoft Academic Search

  \\u000a A large number of families with familial\\u000a isolated hyperparathyroidism (FIHP) have been reported. We wanted to\\u000a determine if some of these families represent early manifestations of\\u000a full-blown syndromes such as multiple endocrine neoplasia type 1\\u000a (MEN-1), as early identification may alter surgical and medical\\u000a management. Four small families with a family history of\\u000a hyperparathyroidism without clear-cut MEN-1 features were

Nancy D. Perrier; Andrea Villablanca; Catharina Larsson; Mariwil Wong; Philip Ituarte; Bin Tean Teh; Orlo H. Clark

2002-01-01

287

Family and nation revisited  

Microsoft Academic Search

Contrary to the promise of the sixties, the condition of families and children in the United State has deteriorated. However, the subject of family policy seems relevant once more. Establishing social policy conducive to the stability and well?being of family life will require an honest addressing of issues including family structure, poverty, drugs, and race. Fiscal policies also must be

Daniel Patrick Moynihan

1990-01-01

288

Black Families. Third Edition.  

ERIC Educational Resources Information Center

The chapters of this collection explore the experiences of black families in the United States and Africa, today and in the past. They are: (1) "African American Families: A Historical Note" (John Hope Franklin); (2) "African American Families and Family Values" (Niara Sudarkasa); (3) "Old-Time Religion: Benches Can't Say 'Amen'" (William Harrison…

McAdoo, Harriette Pipes, Ed.

289

Characteristics of universal embezzling families  

NASA Astrophysics Data System (ADS)

Quantum state embezzlement is the transformation |? >?|? >|? > using only local operations, where |? > and |? > are multipartite quantum states. Exact embezzlement is an impossible task since it implies the increase of entanglement without communication. Surprisingly, van Dam and Hayden [Phys. Rev. A 67, 060302 (2003), 10.1103/PhysRevA.67.060302] find a universal embezzling family of states |? > that enables embezzlement in the bipartite setting with arbitrary precision as the dimension of |? > increases. Furthermore, the family is independent of the state |? > to be embezzled. We study embezzlement in the bipartite setting. We present various requirements and consequences, and infinitely many universal embezzling families inequivalent to that proposed by van Dam and Hayden. We include numerical studies of up to 33-qubit large local systems.

Leung, Debbie; Wang, Bingjie

2014-10-01

290

Family Outcomes: Policy & Practice  

E-print Network

Kansas Division of Early Childhood February 24, 2005 Family Outcomes: Policy & Practice Jean Ann Summers PhD, Beach Center on Disability Nina Zuna Doctoral Student, Beach Center on Disability Kerry Lida Doctoral Student, Beach Center...” of services must be reported IFSP supports family outcomes through… Services to assist families in meeting child needs Measurable results of child and family progress Services in the natural environment Family directed assessment of resources, priorities...

Zuna, Nina

2005-05-05

291

Familial Facial disfigurement in Multiple Familial Trichoepithelioma  

PubMed Central

Trichoepithelioma is an uncommon, benign hamartomatous tumor of the pilosebaceous follicle. Presenting as multiple papules and nodules on face and neck, they pose a significant cosmetic problem in affected individuals. Familial involvement of this dermatosis occurs in an autosomal dominant pattern, the locus being located on chromosome 9p21, which causes multiple facial lesions in family members and their kins. Here, we report a case of multiple familial trichoepithelioma causing considerable disfigurement of the face. PMID:24551711

Kataria, Usha; Agarwal, Deepti; Chhillar, Dinesh

2013-01-01

292

Family allowances and fertility: socioeconomic differences.  

PubMed

This article explores socioeconomic differences in the effect of family allowances on fertility. Although several studies have examined the relationship between cash benefits and fertility, few studies have addressed the possible differential effects of cash benefits on families of different income or education levels. I reconstructed the birth histories of women in the past two Israeli censuses of 1983 and 1995 to study socioeconomic differences in the effect of family allowances up to the seventh parity. The results indicate that family allowances have a significant effect at every parity. Using female education as an indicator of socioeconomic status, I find that socioeconomic status is a significant modifier of the effect of family allowances. Family allowances seem to have a relatively large impact on more-educated women. PMID:19771939

Schellekens, Jona

2009-08-01

293

The lamin protein family.  

PubMed

The lamins are the major architectural proteins of the animal cell nucleus. Lamins line the inside of the nuclear membrane, where they provide a platform for the binding of proteins and chromatin and confer mechanical stability. They have been implicated in a wide range of nuclear functions, including higher-order genome organization, chromatin regulation, transcription, DNA replication and DNA repair. The lamins are members of the intermediate filament (IF) family of proteins, which constitute a major component of the cytoskeleton. Lamins are the only nuclear IFs and are the ancestral founders of the IF protein superfamily. Lamins polymerize into fibers forming a complex protein meshwork in vivo and, like all IF proteins, have a tripartite structure with two globular head and tail domains flanking a central ?-helical rod domain, which supports the formation of higher-order polymers. Mutations in lamins cause a large number of diverse human diseases, collectively known as the laminopathies, underscoring their functional importance. PMID:21639948

Dittmer, Travis A; Misteli, Tom

2011-01-01

294

The lamin protein family  

PubMed Central

Summary The lamins are the major architectural proteins of the animal cell nucleus. Lamins line the inside of the nuclear membrane, where they provide a platform for the binding of proteins and chromatin and confer mechanical stability. They have been implicated in a wide range of nuclear functions, including higher-order genome organization, chromatin regulation, transcription, DNA replication and DNA repair. The lamins are members of the intermediate filament (IF) family of proteins, which constitute a major component of the cytoskeleton. Lamins are the only nuclear IFs and are the ancestral founders of the IF protein superfamily. Lamins polymerize into fibers forming a complex protein meshwork in vivo and, like all IF proteins, have a tripartite structure with two globular head and tail domains flanking a central ?-helical rod domain, which supports the formation of higher-order polymers. Mutations in lamins cause a large number of diverse human diseases, collectively known as the laminopathies, underscoring their functional importance. PMID:21639948

2011-01-01

295

R3Au(6+x)Al26T (R = Ca, Sr, Eu, Yb; T = early transition metal): a large family of compounds with a stuffed BaHg11 structure type grown from aluminum flux.  

PubMed

A collection of new quaternary intermetallic compounds with a cubic, stuffed BaHg(11) structure type has been synthesized by the combination of a divalent rare earth or alkaline earth metal R, an early transition metal T, and gold in an excess of molten aluminum. Structural characterization of these R(3)Au(6+x)Al(26)T compounds by powder and single crystal X-ray diffraction indicates that the unit cell varies with the radii of the early transition metal T and the rare earth/alkaline earth R as expected. The element T (where T = group 4, 5, 6, and 7 element) appears to be responsible for the stabilization of up to 43 different members of the R(3)Au(6+x)Al(26)T family of compounds. Varying amounts of disorder and trends in partial occupancies of the Au stuffed site--the site that is vacant in the parent compound BaHg(11)--are also indicated by the diffraction studies of this family of compounds. Magnetic susceptibility data reveals that the transition metal atoms in these materials do not possess local magnetic moments. For the magnetic rare earth containing materials, the europium compounds undergo a ferromagnetic transition at 10 K, and the ytterbium analogues show mixed valent behavior. Band structure calculations also support a mixed valent state for Yb in these compounds. PMID:19146424

Latturner, Susan E; Bilc, Daniel; Mahanti, S D; Kanatzidis, Mercouri G

2009-02-16

296

Novel Deletion of SERPINF1 Causes Autosomal Recessive Osteogenesis Imperfecta Type VI in Two Brazilian Families.  

PubMed

Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease. PEDF is a secreted glycoprotein of the serpin superfamily that maintains bone homeostasis and regulates osteoid mineralization, and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860). Here, we report a consanguineous Brazilian family in which multiple individuals from at least 4 generations are affected with a severe form of OI, and we also report an unrelated individual from the same small city in Brazil with a similar but more severe phenotype. In both families the same homozygous SERPINF1 19-bp deletion was identified which is not known in the literature yet. We described intra- and interfamilial clinical and radiological phenotypic variability of OI type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in the literature are reviewed. PMID:25565926

Minillo, Renata Moldenhauer; Sobreira, Nara; de Faria Soares, Maria de Fatima; Jurgens, Julie; Ling, Hua; Hetrick, Kurt N; Doheny, Kimberly F; Valle, David; Brunoni, Decio; Perez, Ana B Alvarez

2014-12-01

297

Novel Deletion of SERPINF1 Causes Autosomal Recessive Osteogenesis Imperfecta Type VI in Two Brazilian Families  

PubMed Central

Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease. PEDF is a secreted glycoprotein of the serpin superfamily that maintains bone homeostasis and regulates osteoid mineralization, and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860). Here, we report a consanguineous Brazilian family in which multiple individuals from at least 4 generations are affected with a severe form of OI, and we also report an unrelated individual from the same small city in Brazil with a similar but more severe phenotype. In both families the same homozygous SERPINF1 19-bp deletion was identified which is not known in the literature yet. We described intra- and interfamilial clinical and radiological phenotypic variability of OI type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in the literature are reviewed.

Minillo, Renata Moldenhauer; Sobreira, Nara; de Faria Soares, Maria de Fatima; Jurgens, Julie; Ling, Hua; Hetrick, Kurt N.; Doheny, Kimberly F.; Valle, David; Brunoni, Decio; Perez, Ana B. Alvarez

2014-01-01

298

Topic in Depth - Asteraceae, a.k.a. Sunflower Family  

NSDL National Science Digital Library

The Family Asteraceae (a.k.a. Compositae, Composite, Sunflower, Aster) is an impressively large and diverse family of flowering plants (circa 20,000 species). This Topic in Depth offers an assemblage of sites that provide images of, and introductory information about, this remarkable family.

2010-09-15

299

Family Therapy for the "Truncated" Nuclear Family.  

ERIC Educational Resources Information Center

The truncated nuclear family consists of a two-generation group in which conflict has produced a polarization of values. The single-parent family is at special risk. Go-between process enables the therapist to depolarize sharply conflicted values and reduce pathogenic relating. (Author)

Zuk, Gerald H.

1980-01-01

300

Family assessment: Centripetal and centrifugal family systems  

Microsoft Academic Search

A consideration of interactional style is useful to both researchers and clinicians interested in family assessment. This paper offers data and process evaluation scales designed to determine family interactional style, conceptualized as a continuum ranging from centripetal (CP) to centrifugal (CF), and containing at the midpoint a mixed area in which facets of both the CP and the CF styles

Martha Kelsey-smith; W. Robert Beavers M. D

1981-01-01

301

Families of minor planets  

NASA Technical Reports Server (NTRS)

Physical studies of individual family members show that at least the Themis, Eos, Koronis, Nysa/Hertha, and Budrosa families of minor planets are the result of the breakup of discrete parent bodies. Only a few families have been studied in detail, and even in those few cases, the full force of observational techniques has not been applied. Crucial for the understanding of families and their parent bodies are detailed physical studies of family members; precise mineralogical interpretation of observational data to identify the geochemistry of the parent bodies; and studies of the collisional evolution of family members.

Gradie, J. C.; Chapman, C. R.; Williams, J. G.

1979-01-01

302

[Familial hypocalciuric hypercalcemia. A new family].  

PubMed

A new example of familial hypocalciuric hypercalcaemia is reported. The family studied consists of 19 members over four generations. The first patient described in this study had already undergone a classical surgical operation for "primary hyperparathyroidism" before the correct diagnosis was established: that of a new syndrome described for the first time by Foley in 1972 and subsequently studied by Marx since 1977. The features of this syndrome are: hypercalcaemia accompanied by hypocalciuria, autosomal dominant transmission with strong penetrance, with early appearance of hypercalcaemia, absence of signs of familial multiple endocrine neoplasia, benign course and persistence of the hypercalcaemia despite classical sub-total parathyroidectomy. Following a family survey, the authors discovered eight other members of the family who also presented this syndrome. PMID:4081583

Langhendries, J P; Chanoine, F; Corvilain, J; Fuss, M; Van Geertruyden, J

1985-11-01

303

Segregation of a Latent High Adiposity Phenotype in Families with a History of Type 2 Diabetes Mellitus Implicates Rare Obesity-Susceptibility Genetic Variants with Large Effects in Diabetes-Related Obesity  

PubMed Central

Background We recently reported significantly greater weight gain in non-diabetic healthy subjects with a 1st degree family history (FH+) of type 2 diabetes mellitus (T2DM) than in a matched control group without such history (FH?) during voluntary overfeeding, implying co-inheritance of susceptibilities to T2DM and obesity. We have estimated the extent and mode of inheritance of susceptibility to increased adiposity in FH+. Methods Normoglycaemic participants were categorised either FH+ (?1 1st degree relative with T2DM, 50F/30M, age 45±14 (SD) yr) or FH? (71F/51M, age 43±14 yr). Log-transformed anthropometric measurements (height, hip and waist circumferences) and lean, bone and fat mass (Dual Energy X-ray Absorptiometry) data were analysed by rotated Factor Analysis. The age- and gender-adjusted distributions of indices of adiposity in FH+ were assessed by fits to a bimodal model and by relative risk ratios (RR, FH+/FH?) and interpreted in a purely genetic model of FH effects. Results The two orthogonal factors extracted, interpretable as Frame and Adiposity accounted for 80% of the variance in the input data. FH+ was associated with significantly higher Adiposity scores (p<0.01) without affecting Frame scores. Adiposity scores in FH+ conformed to a bimodal normal distribution, consistent with dominant expression of major susceptibility genes with 59% (95% CI 40%, 74%) of individuals under the higher mode. Calculated risk allele frequencies were 0.09 (0.02, 0.23) in FH?, 0.36 (0.22, 0.48) in FH+ and 0.62 (0.36, 0.88) in unobserved T2DM-affected family members. Conclusions The segregation of Adiposity in T2DM-affected families is consistent with dominant expression of rare risk variants with major effects, which are expressed in over half of FH+ and which can account for most T2DM-associated obesity in our population. The calculated risk allele frequency in FH? suggests that rare genetic variants could also account for a substantial fraction of the prevalent obesity in this society. PMID:23950934

Jenkins, Arthur B.; Batterham, Marijka; Samocha-Bonet, Dorit; Tonks, Katherine; Greenfield, Jerry R.; Campbell, Lesley V.

2013-01-01

304

The 1993 Family Day Care Licensing Study. Family Day Care Advocacy Project.  

ERIC Educational Resources Information Center

This study contains the results of a nationwide survey of state regulatory agencies conducted to update family day care licensing information gathered in 1992. Following a list of definitions for terms used in the study and a brief overview of each state's regulatory requirements for small and large family day care providers, the main section…

Children's Foundation, Washington, DC.

305

Stewardship vs. Stagnation: An Empirical Comparison of Small Family and Non-Family Businesses &ast  

Microsoft Academic Search

abstract? Two major perspectives can be construed in the literature concerning the nature of family owned businesses (FOBs). The first implies that these enterprises have unique characteristics of stewardship. FOB owners are said to care deeply about the long-term prospects of the business, in large part because their family's fortune, reputation and future are at stake. Their stewardship is said

Danny Miller; Isabelle Le Breton-Miller; Barry Scholnick

2008-01-01

306

Contacting My Donor Family  

MedlinePLUS

... Donor Family Newsroom Minorities Contacting My Donor Family Writing anything can be a challenge. Staring at a ... can take to get started. The process of writing your letter may take some time, but at ...

307

The Changing American Family.  

ERIC Educational Resources Information Center

Reviews recent statistics which demonstrate how different modern families are from the stereotyped model American nuclear family. Provides suggestions for elementary social studies teachers and includes an annotated bibliography of instructional resources. (JDH)

Joseph, Pamela B.

1986-01-01

308

Strengthening Our Military Families  

MedlinePLUS

... to quality child care remains a focus of leadership and families across the Armed Forces. Military families ... an expert in military issues to make a difference. Every American can do something.” —Michelle Obama and ...

309

Familial Periodic Paralyses  

MedlinePLUS

NINDS Familial Periodic Paralyses Information Page Synonym(s): Periodic Paralyses Table of Contents (click to jump to sections) What are Familial Periodic Paralyses? Is there any treatment? What is the prognosis? What research is ...

310

Managing Your Family Business  

E-print Network

L-5437 2-03 Managing Your Family Business Danny Klinefelter Professor and Extension Economist Texas Cooperative Extension The Texas A&M University System Successful management of a family business involves six characteristics: ? Shared vision...

Klinefelter, Danny A.

2003-04-14

311

Importance of Family Routines  

MedlinePLUS

... Caregivers and Teachers (PedFACTs) Participant Manual Pediatric First Aid for Caregivers and Teachers (PedFACTs) Teaching Package Allergies and Asthma Family Life Health Management - Medical Home Family Dynamics Adoption & Foster Care Communication & ...

312

Family Life Cycle Stages  

Microsoft Academic Search

Individual life stages happen within the context of family life. This article describes Betty Carter's and Monica McGoldrick's Family Life Cycle stages as a context for Eric Erikson's stages of psychosocial development, Daniel Levinson's Stages of a Man's Life, and Jean Piaget's stages of cognitive development. The author juxtaposes the tasks of each family life stage with the individual life

M. A. Armour

1995-01-01

313

Year of the Family.  

ERIC Educational Resources Information Center

This special issue focuses on problems and challenges confronting the California family and on research and extension efforts to provide at least partial answers. Research briefs by staff include "Challenges Confront the California Family" (state trends in poverty, divorce, single-parent families, child abuse, delinquency, teen births, limited…

California Agriculture, 1994

1994-01-01

314

Familial Cholestatic Syndromes  

Microsoft Academic Search

The term ‘familial’ is an unfortunate one. Although the definition includes ‘hereditary’, the inference is that it will usually have occurred in other family members. For many of the conditions described in this article this is often not the case, and for this reason, ‘familial’ conditions may be overlooked when reaching a diagnosis. Cholestasis is defined differently by clinicians, pathologists

Richard Thompson

2008-01-01

315

Strengthening America's Families.  

ERIC Educational Resources Information Center

Improving parenting practices and the family environment is the most effective, enduring strategy for combating juvenile delinquency. Describes the Office of Juvenile Justice and Delinquency Prevention's Strengthening America's Families Initiative. Highlights several family-focused prevention programs identified as exemplary, explaining how they…

Alvarado, Rose; Kumpfer, Karol

2000-01-01

316

Familial progressive supranuclear palsy  

Microsoft Academic Search

A progressive extrapyramidal syndrome and dementia occurred in three members of one family. The age of onset was in the seventh decade and the affected individuals showed many of the clinical features of progressive supranuclear palsy (PSP). Necropsy of one individual revealed the neuropathological features of PSP. We propose that this family has a familial form of PSP and review

J Brown; P Lantos; M Stratton; P Roques; M Rossor

1993-01-01

317

Family Housing and Services.  

ERIC Educational Resources Information Center

Recognizing the need for a strong family housing program to support a student body composed of many nontraditional students, Texas Woman's University converted a traditional residence hall into a family housing unit with an after-school and summer recreation program. The majority of residents in family housing are single mothers with children who…

Murphy-Chadwick, Nancy; And Others

318

Resilience in Remarried Families  

Microsoft Academic Search

The present study aims to identify those resilience factors that enable remarried families to withstand and rebound from the disruptive challenges they face. A parent and a child from 38 families independently completed seven questionnaires and answered an open-ended question. The following resilience-associated factors were identified: (1) supportive family relationships, (2) affirming and supportive communication, (3) a sense of control

Abraham P. Greeff; Carien Du Toit

2009-01-01

319

Families and Fragile Syndrome  

E-print Network

Families and Fragile Syndrome U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH Health and Human Development (NICHD) family album about Fragile X syndrome. As a health research agency is designed to give you and your family some general information about Fragile X syndrome, its causes, its

Rau, Don C.

320

Fatherhood and Family Support.  

ERIC Educational Resources Information Center

On the assumption that fathers have been relatively absent from family support programs, this publication of the Family Resource Coalition addresses the role of fathers in family support programs, examines the impact of fathers on their children, and describes programs involving fathers successfully. Articles include: (1) "What's Behind the…

Goetz, Kathy, Ed.

1996-01-01

321

The Family Farm Project  

NSDL National Science Digital Library

Kenyon College's Family Farm Project, "a three-year study exploring family farming and community life in Knox County, Ohio," presents an intimate multimedia view of the daily life of the family farm, which some consider a vanishing institution in America.

1996-01-01

322

Employment Characteristics of Families  

NSDL National Science Digital Library

The Bureau of Labor Statistics site offers data on the employment characteristics of American families. The statistics include data on employment and unemployment in families by race, relationship, sex, marital status, presence of children in the family, and presence of children under three, among others. The data can be accessed from a table of contents or reviewed in an extensive news release.

2001-01-01

323

Families in Transition.  

ERIC Educational Resources Information Center

This issue of "Emphasis" deals with families in transition, providing some model programs for the new family and some historical perspectives on how families have developed over time. Articles include: (1) "Nostalgia on the Right" (Nancy Theriot); (2) "Heart to Heart" (Nancy Harrington-MacLennan); (3) "The Media Get the Message" (Janet Alyn); (4)…

Britton, Patti O., Ed.; McGee, Michael, Ed.

1987-01-01

324

Learning from Latino Families  

ERIC Educational Resources Information Center

As a researcher in parent engagement in school and former parent activist, the author shares three lessons for sparking more authentic partnerships between schools and immigrant families. First, schools need to move away from deficit thinking and validate families' cultures. In the case of Latino immigrant families, this entails understanding…

Auerbach, Susan

2011-01-01

325

Family Violence: An Overview.  

ERIC Educational Resources Information Center

Family violence is a widespread problem; research has shown multiple factors are associated with family violence. Types of family violence include spouse abuse; elder abuse and neglect; child abuse and neglect; parent abuse; and sibling abuse. There are three types of spouse abuse: physical abuse, sexual violence, and psychological/emotional…

National Center on Child Abuse and Neglect (DHHS/OHDS), Washington, DC.

326

Adlerian Family Counseling.  

ERIC Educational Resources Information Center

Describes a model of family counseling based on Adlerian psychology. A brief overview of the psychological principles of Adlerian psychology is provided as well as an intervention schema to help the elementary counselor decide what family members to include in counseling and how to deal ethically with families. (RC)

Kern, Roy M.; Carlson, Jon

1981-01-01

327

Families and Assisted Living*  

PubMed Central

Purpose Despite growing research on assisted living (AL) as a residential care option for older adults, the social ramifications of residents' transitions to assisted living is relatively unexplored. This article examines family involvement in AL, including family structures of residents, types of involvement from family members living outside the AL, and outcomes for these family members. Design and Methods We reviewed current literature utilizing the MEDLINE, PSYCINFO, and CINAHL databases to identify AL studies that examined issues pertaining to families or informal care. Following the screening of abstracts, 180 reports were retrieved for further review, and 62 studies were selected for inclusion. Results Families visit residents frequently and provide a wide range of instrumental assistance but provide only minimal personal care. Studies of family outcomes indicated relatively high satisfaction, but potential care burden as well. Implications How family care and involvement occurs in AL in relation to formal care provision and whether various types of formal-informal care integration influence family outcomes remains unclear. We suggest a research agenda that attempts to tease out causal relationships for family involvement, differentiate family roles, and implement longitudinal analyses for a range of family outcomes. PMID:18162571

Gaugler, Joseph E.; Kane, Robert L.

2008-01-01

328

The Family Leukemia Association  

ERIC Educational Resources Information Center

An association of families of children with leukemia, the Family Leukemia Association (FLA), was recently established in Toronto. This paper discusses (a) philosophy of the FLA; (b) formative years of this organization; (c) problems encountered by leukemic children and their families; and (d) the FLA's past and future educational and social…

Pollitt, Eleanor

1976-01-01

329

Toward the Postmodern Family  

ERIC Educational Resources Information Center

Examines three aspects of family life that are evolving in directions that have no historical precedent--adolescent indifference to the family's identity that shows up in the discontinuity of values from parents to children, instability in the life of the couple, and systematic demolition of the nuclear family. (Author/IRT)

Shorter, Edward

1976-01-01

330

Novel CLDN14 Mutations in Pakistani Families With Autosomal Recessive Non-Syndromic Hearing Loss  

PubMed Central

Mutations in the CLDN14 gene are known to cause autosomal recessive (AR) non-sydromic hearing loss (NSHL) at the DFNB29 locus on chromosome 21q22.13. As part of an ongoing study to localize and identify NSHL genes, the ARNSHL segregating in four Pakistani consanguineous families were mapped to the 21q22.13 region with either established or suggestive linkage. Given the known involvement of CLDN14 gene in NSHL, DNA samples from hearing-impaired members from the four families were sequenced to potentially identify causal variants within this gene. Three novel CLDN14 mutations, c.167G>A (p.Trp56?), c.242G>A (p.Arg81His), and c.694G>A (p.Gly232Arg), segregate with hearing loss (HL) in three of the families. The previously reported CLDN14 mutation c.254T>A (p.Val85Asp) was observed in the fourth family. None of the mutations were detected in 400 Pakistani control chromosomes and all were deemed damaging based on bioinformatics analyses. The nonsense mutation c.167G>A (p.Trp56?) is the first stop codon mutation in CLDN14 gene to be identified to cause NSHL. The c.242G>A (p.Arg81His) and c.694G>A (p.Gly232Arg) mutations were identified within the first extracellular loop and the carboxyl-tail of claudin-14, respectively, which highlights the importance of the extracellular domains and phosphorylation of cytoplasmic tail residues to claudin function within the inner ear. The HL due to novel CLDN14 mutations is prelingual, severe-to-profound with greater loss in the high frequencies. PMID:22246673

Lee, Kwanghyuk; Ansar, Muhammad; Andrade, Paula B.; Khan, Bushra; Santos-Cortez, Regie Lyn P.; Ahmad, Wasim; Leal, Suzanne M.

2012-01-01

331

PARK20 caused by SYNJ1 homozygous Arg258Gln mutation in a new Italian family.  

PubMed

SYNJ1 has been recently identified by two independent groups as the gene defective in a novel form of autosomal recessive, early-onset atypical parkinsonism (PARK20). Two consanguineous families were initially reported (one of Sicilian and one of Iranian origins), with the same SYNJ1 homozygous mutation (c.773G?>?A, p.Arg258Gln) segregating with a similar phenotype of early-onset parkinsonism and additional atypical features. Here, we report the identification of the same SYNJ1 homozygous mutation in two affected siblings of a third pedigree. Both siblings had mild developmental psychomotor delay, followed, during the third decade of life, by progressive parkinsonism, dystonia, and mild cognitive impairment. One sibling suffered one episode of generalized seizures. Neuroimaging studies revealed severe nigrostriatal dopaminergic defects, mild striatal and very mild cortical hypometabolism. Treatment with dopamine agonists and anticholinergics resulted in partial improvements. Genetic analyses revealed in both siblings the SYNJ1 homozygous c.773G?>?A (p.Arg258Gln) mutation. Haplotype analysis suggests that the mutation has arisen independently in this family and the Sicilian PARK20 family previously described by us, in keeping with the hypothesis of a mutational hot spot. This is the third reported family with autosomal recessive, early-onset parkinsonism associated with the SYNJ1 p.Arg258Gln mutation. This work contributes to the definition of the genetic and clinical aspects of PARK20. This newly recognized form must be considered in the diagnostic work-up of patients with early-onset atypical parkinsonism. The presence of seizures might represent a red flag to suspect PARK20. PMID:24816432

Olgiati, Simone; De Rosa, Anna; Quadri, Marialuisa; Criscuolo, Chiara; Breedveld, Guido J; Picillo, Marina; Pappatà, Sabina; Quarantelli, Mario; Barone, Paolo; De Michele, Giuseppe; Bonifati, Vincenzo

2014-08-01

332

Family Fitness = Family Fun! Presented by  

E-print Network

health benefits 35% of adults 18 years and older who engaged in regular leisure-time physical activity calories! · Build family bonds & create memories · Experience love and laughter · Master new skills. #12

333

Family Literacy Schools, teachers and  

E-print Network

1 Family Literacy Schools, teachers and family literacy . . . . . . . . . . . . . . 4 A snapshot of National Family Literacy . . . . . . . . . . . . . 6 A representative community organization . . . 7 Supporting regional cooperation . . . . . . . . . . . . . . . 8 Family Literacy: Programming that Works

Ellis, Randy

334

Further evidence on family change in Papua New Guinea.  

PubMed

This paper attempts to elaborate on previous papers on family change in postwar urban Papua New Guinea and to point out the implications of the emerging patterns as they relate to demands likely to be made on existing government programs in future years. There has been rapid growth of an educated, urban resident population, with the use of wages and cash much more prevalent than before. There is some attenuation of family ties with more emphasis on the nuclear family, which is likely to be smaller than the traditional, large family. In rural areas people prefer large families. There continues to be use of contraception and family planning, an extension of traditional means of controlling reproductive behavior. The impact of social implications of weakened family ties on government programs is marginal. It is clear, however, that there is likely to be substantial growth in the urban population (3.8%/year based on 1971 mortality levels) because of rapid declines in death rates. This will make it more difficult for government to provide health care, education and employment for the population, especially young people. Tables give statistics on 1) family type by education for male heads of households, 2) preference of male respondents for a large or small family, 3) desired number of children by education, male and female respondents, 4) attitudes toward family limitation by education, male respondents, 5) use of family planning by education, female respondents, and 6) population characteristics implied by 1971 levels of fertility and mortality. PMID:12265175

Mcdevitt, T M

1980-01-01

335

The Fungal Defensin Family Enlarged  

PubMed Central

Fungi are an emerging source of peptide antibiotics. With the availability of a large number of model fungal genome sequences, we can expect that more and more fungal defensin-like peptides (fDLPs) will be discovered by sequence similarity search. Here, we report a total of 69 new fDLPs encoded by 63 genes, in which a group of fDLPs derived from dermatophytes are defined as a new family (fDEF8) according to sequence and phylogenetic analyses. In the oleaginous fungus Mortierella alpine, fDLPs have undergone extensive gene expansion. Our work further enlarges the fungal defensin family and will help characterize new peptide antibiotics with therapeutic potential. PMID:25230677

Wu, Jiajia; Gao, Bin; Zhu, Shunyi

2014-01-01

336

Familial germ cell tumor  

PubMed Central

Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presence of germ cell malignancies in the siblings of different sex in the same family points toward a genetic susceptibility. Literature review revealed only six similar cases. A discussion regarding the rare occurrence of familial germ cell malignancies with the affected family members may be worthwhile. PMID:22754236

Cyriac, Sanju; Rajendranath, Rejeev; Louis, A Robert; Sagar, T. G.

2012-01-01

337

Putting 'family' back in family planning.  

PubMed

Family planning visits are designed to help women build families in a manner most compatible with their life goals. Women's knowledge regarding age-related fertility is suboptimal, and first wanted pregnancies are now occurring at older ages. Here we review the issue of diminishing chances of a pregnancy occurring in women over 30 years of age. A debate arises over whether to perform a standard fertility assessment at an age when, for example, oocyte freezing is still practical and feasible, knowing that the proven predictors in subfertile couples may be less informative, or even inappropriate, in women without complaints about fertility. Studies have demonstrated that if women knew that their fertility was diminishing, they might alter life plans, including having children sooner or considering oocyte preservation. Therefore, we argue that physicians need to make an effort to evaluate a woman's childbearing priorities, though not necessarily their fertility, during the initial family planning visit. PMID:25406182

Seifer, David B; Minkoff, Howard; Merhi, Zaher

2015-01-01

338

Neighborhoods and Families  

Microsoft Academic Search

\\u000a Neighborhoods have a profound impact on children and their families, including health and safety, educational attainment,\\u000a child maltreatment risk, and many others. Yet, surprisingly little is known about the specific mechanisms through which neighborhood\\u000a physical and social characteristics features influence child and family outcomes. This chapter looks at current definitions\\u000a for community and family and reviews research for community effects

James R. McDonell

339

The family lecture.  

PubMed

SUMMARY This paper describes a lecture about my extended family, in which I discuss a variety of configurations consisting of lesbian, gay, and bisexual adults, and our children. It raises an array of issues, including alternative insemination, biological and nonbiological parentage, donors and birthmothers, adoption, co-parenting and blended families, significant others, and gay marriage and domestic partnership. It helps many students obtain both a more expansive sense of family and adeeper understanding of homophobia. PMID:24804601

Rose, Nancy E

2002-10-01

340

Large Scale RNAi Screen Reveals That the Inhibitor of DNA Binding 2 (ID2) Protein Is Repressed by p53 Family Member p63 and Functions in Human Keratinocyte Differentiation*  

PubMed Central

The inhibitor of DNA binding 2, dominant negative helix-loop-helix protein, ID2, acts as an oncogene and elevated levels of ID2 have been reported in several malignancies. Whereas some inducers of the ID2 gene have been characterized, little is known regarding the proteins capable to repress its expression. We developed siRNA microarrays to perform a large scale loss-of-function screen in human adult keratinocytes engineered to express GFP under the control of the upstream region of ID2 gene. We screened the effect of siRNA-dependent inhibition of 220 cancer-associated genes on the expression of the ID2::GFP reporter construct. Three genes NBN, RAD21, and p63 lead to a repression of ID2 promoter activity. Strikingly NBN and RAD21 are playing on major role in cell cycle progression and mitosis arrest. These results underline the pregnant need to silence ID2 expression at transcript level to promote cell cycle exit. Central to this inhibitory mechanism we find p63, a key transcription factor in epithelial development and differentiation, which binds specific cis-acting sequence within the ID2 gene promoter both in vitro and in vivo. P63 would not suppress ID2 expression, but would rather prevent excessive expression of that protein to enable the onset of keratinocyte differentiation. PMID:21478550

Wu, Ning; Castel, David; Debily, Marie-Anne; Vigano, Maria Alessandra; Alibert, Olivier; Mantovani, Roberto; Iljin, Kristina; Romeo, Paul-Henri; Gidrol, Xavier

2011-01-01

341

Deletion mutation in BSCL2 gene underlies congenital generalized lipodystrophy in a Pakistani family  

PubMed Central

Background Congenital generalized lipodystrophy (CGL) also known as Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a genetically heterogeneous disorder characterized by loss of adipose tissues, Acanthosis nigricans, diabetes mellitus, muscular hypertrophy, hepatomegaly and hypertriglyceridemia. There are four subclinical phenotypes of CGL (CGL1-4) and mutations in four genes AGPAT2, BSCL2, CAV1 and PTRF have been assigned to each type. Methods The study included clinical and molecular investigations of CGL disease in a consanguineous Pakistani family. For mutation screening all the coding exons including splice junctions of AGPAT2, BSCL2, CAV1 and PTRF genes were PCR amplified and sequenced directly using an automated DNA sequencer ABI3730. Results Sequence analysis revealed a single base pair deletion mutation (c.636delC; p.Tyr213ThrfsX20) in exon 5 of BSCL2 gene causing a frame shift and premature termination codon. Conclusion Mutation identified here in BSCL2 gene causing congenital generalized lipodystrophy is the first report in Pakistani population. The patients exhibited characteristic features of generalized lipodystrophy, Acanthosis nigricans, diabetes mellitus and hypertrophic cardiomyopathy. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1913913076864247. PMID:23659685

2013-01-01

342

Insulin-dependent diabetes mellitus in children: Familial and clinical patterns in Riyadh.  

PubMed

Type I diabetes mellitus is probably common in Saudi Arabia, but only a small amount of information on the disease is available and most cases reported so far have been type II diabetes mellitus. Type I diabetes was diagnosed in 110 children who were followed at Suleimania Children's Hospital over a five-year period (1985-1989). Saudis represented 74.5% (82/110) of the patients, and 53.6% (59/110) were female. Consanguinity existed in 42.7% (47/110) of the parents. A first-degree family history was positive for insulin-dependent diabetes mellitus in 28.1% (31/110). Mean age at onset was 5.87 years, which is low compared with other ages cited in the literature. Thirty-three patients (30%) were below three years of age at onset. The most common clinical sign was diabetic ketoacidosis, which was seen in 67.2% (74/110). Duration of symptoms before diagnosis ranged from two days to more than two months, with a mean of 18.2 days. Partial remission was seen in 30.9% (34/110). This low percentage is probably due to the young age distribution at onset and perhaps to a different pattern of severity of the disease in our community. Further studies, including opening a local registry, are needed for confirming the incidence and characteristics of the disease in Saudi Arabia. PMID:17588108

Salman, H; Abanamy, A; Ghassan, B; Khalil, M

1991-05-01

343

Whole exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome.  

PubMed

Context: Pituitary stalk interruption syndrome (PSIS) is a rare congenital anomaly of the pituitary gland characterized by pituitary gland insufficiency, thin or discontinuous pituitary stalk, anterior pituitary hypoplasia, and ectopic positioning of the posterior pituitary gland (neurohypophysis). The clinical presentation of patients with PSIS varies from isolated growth hormone (GH) deficiency to combined pituitary insufficiency and accompanying extrapituitary findings. Mutations in HESX1, LHX4, OTX2, SOX3, and PROKR2 have been associated with PSIS in less than 5% of cases; thus, the underlying genetic etiology for the vast majority of cases remains to be determined. Objective: We applied whole exome sequencing to a consanguineous family with two affected siblings who have pituitary gland insufficiency and radiographic findings of hypoplastic (thin) pituitary gland, empty sella, ectopic neurohypophysis, and interrupted pitiutary stalk - characteristic clinical diagnostic findings of PSIS. Design and Participants: Targeted whole exome sequencing (WES) was applied to two affected and one unaffected siblings. Results: WES of two affected and one unaffected sibling revealed a unique homozygous missense mutation in GPR161, which encodes the orphan G-protein-coupled receptor 161, a protein responsible for transducing extracellular signals across the plasma membrane into the cell. Conclusion: Mutations of GPR161 may be implicated as a potential novel cause of PSIS. PMID:25322266

Karaca, Ender; Buyukkaya, Ramazan; Pehlivan, Davut; Charng, Wu-Lin; Yaykasli, Kursat O; Bayram, Yavuz; Gambin, Tomasz; Withers, Marjorie; Atik, Mehmed M; Arslanoglu, Ilknur; Bolu, Semih; Erdin, Serkan; Buyukkaya, Ayla; Yaykasli, Emine; Jhangiani, Shalini N; Muzny, Donna M; Gibbs, Richard A; Lupski, James R

2014-10-16

344

A Mutation in HOXA2 Is Responsible for Autosomal-Recessive Microtia in an Iranian Family  

PubMed Central

Microtia, a congenital deformity manifesting as an abnormally shaped or absent external ear, occurs in one out of 8,000–10,000 births. We ascertained a consanguineous Iranian family segregating with autosomal-recessive bilateral microtia, mixed symmetrical severe to profound hearing impairment, and partial cleft palate. Genome-wide linkage analysis localized the responsible gene to chromosome 7p14.3-p15.3 with a maximum multi-point LOD score of 4.17. In this region, homeobox genes from the HOXA cluster were the most interesting candidates. Subsequent DNA sequence analysis of the HOXA1 and HOXA2 homeobox genes from the candidate region identified an interesting HOXA2 homeodomain variant: a change in a highly conserved amino acid (p.Q186K). The variant was not found in 231 Iranian and 109 Belgian control samples. The critical contribution of HoxA2 for auditory-system development has already been shown in mouse models. We built a homology model to predict the effect of this mutation on the structure and DNA-binding activity of the homeodomain by using the program Modeler 8v2. In the model of the mutant homeodomain, the position of the mutant lysine side chain is consistently farther away from a nearby phosphate group; this altered position results in the loss of a hydrogen bond and affects the DNA-binding activity. PMID:18394579

Alasti, Fatemeh; Sadeghi, Abdorrahim; Sanati, Mohammad Hossein; Farhadi, Mohammad; Stollar, Elliot; Somers, Thomas; Van Camp, Guy

2008-01-01

345

Family Literacy: Abstracts of Family Literacy Programs.  

ERIC Educational Resources Information Center

The abstracts in this publication describe 29 federally and privately funded family literacy projects in the United States. Each entry provides the name of the project, background information, project aims, and the names, addresses, and telephone numbers of contact persons. (RH)

Office of Vocational and Adult Education (ED), Washington, DC. Div. of Adult Education and Literacy.

346

The Pfam Protein Families Database  

Microsoft Academic Search

ABSTRACT Pfam is a ,large collection of protein multiple sequence alignments and profile hidden Markov models. Pfam is available on the World Wide Web in the UK at http:\\/\\/www.sanger.ac.uk\\/Software\\/Pfam\\/, in Sweden at http:\\/\\/www.cgb.ki.se\\/Pfam\\/, in France at http:\\/\\/pfam.jouy.inra.fr\\/ and in the ,US at http:\\/\\/ pfam.wustl.edu\\/. The latest version (6.6) of Pfam contains 3071 families, which match 69% of proteins inSWISS-PROT 39

Alex Bateman; Ewan Birney; Lorenzo Cerutti; Richard Durbin; Laurence Ettwiller; Sean R. Eddy; Sam Griffiths-jones; Kevin L. Howe; Mhairi Marshall; Erik L. L. Sonnhammer

2002-01-01

347

The Pfam Protein Families Database  

Microsoft Academic Search

Pfam is a large collection of protein multiple sequence alignments and profile hidden Markov models. Pfam is available on the World Wide Web in the UK at http:\\/\\/www.sanger.ac.uk\\/Software\\/Pfam\\/, in Sweden at http:\\/\\/www.cgb.ki.se\\/Pfam\\/, in France at http:\\/\\/pfam.jouy.inra.fr\\/ and in the US at http:\\/\\/ pfam.wustl.edu\\/. The latest version (6.6) of Pfam contains 3071 families, which match 69% of proteins in SWISS-PROT 39

Alex Bateman; Ewan Birney; Lorenzo Cerruti; Richard Durbin; Laurence Etwiller; Sean R. Eddy; Sam Griffiths-Jones; Kevin L. Howe; Mhairi Marshall; Erik L. L. Sonnhammer

2001-01-01

348

Familial Aggregation of Glioma: A Pooled Analysis  

PubMed Central

In genome-wide association studies, inherited risk of glioma has been demonstrated for rare familial syndromes and with common variants from 3–5 chromosomal regions. To assess the degree of familial aggregation of glioma, the authors performed a pooled analysis of data from 2 large glioma case-control studies in the United States (MD Anderson Cancer Center, Houston, Texas (1994–2006) and University of California, San Francisco (1991–2004)) and from the Swedish Cancer Registry (1958–2006) to measure excess cases of cancer among first-degree relatives of glioma probands. This analysis included 20,377 probands with glioma and 52,714 first-degree relatives. No overall increase was found in the expected number of cancers among family members; however, there were 77% more gliomas than expected. There were also significantly more sarcoma and melanoma cases than expected, which is supported by evidence in the literature, whereas there were significantly fewer-than-expected cases of leukemia, non-Hodgkin lymphoma, and bladder, lung, pancreatic, prostate, and uterine cancers. This large pooled analysis provided sufficient numbers of related family members to examine the genetic mechanisms involved in the aggregation of glioma with other cancers in these families. However, misclassification due to unvalidated cancers among family members could account for the differences seen by study site. PMID:20858744

Scheurer, Michael E.; Etzel, Carol J.; Liu, Mei; Barnholtz-Sloan, Jill; Wiklund, Fredrik; Tavelin, Björn; Wrensch, Margaret R.; Melin, Beatrice S.; Bondy, Melissa L.

2010-01-01

349

A missense mutation (p.G274R) in gene ASPA causes Canavan disease in a Pakistani family.  

PubMed

Canavan disease (OMIM 271900) is an autosomal recessive lethal neurodegenerative disorder characterized by spongy degeneration of the brain. A highly consanguineous Pakistani family with Canavan disease was enrolled on the basis of diagnosis. All the affected individuals have mental retardation, megalocephaly and degradation of motor skills, poor head control, partial vision loss, weakness of the muscles and raised urinary concentration of N-acetyl aspartic acid in the urine. Blood samples were collected from affected as well as normal siblings and processed for DNA purification. Linkage analysis was performed by typing three short tandem repeat markers D17S1583 (7.19 cM), D17S1828 (10.02 cM) and D17S919 (14.69 cM) for an already-reported gene/locus ASPA at chromosome 17p13.2 causing Canavan disease. During linkage analysis, all the affected individuals were homozygous for short tandem repeat markers while the normal siblings were heterozygous showing co-segregation of the disease. Gene ASPA (NM_000049) was undertaken to sequence for mutation analysis. As a result of sequence analysis, we found missense substitution 740A?G (p.G274R) in exon 6 of gene ASPA. To our knowledge, this is the first report about Canavan disease on a Pakistani family. PMID:22219087

Hussain, Rashida; Daud, Shakeela; Kakar, Naseebullah; Ahmad, Adeel; Baloch, Abdul Hameed; Tareen, Abdul Malik; Kakar, Muhammad Azam; Ahmad, Jamil

2012-05-01

350

Robertsonian translocation between chromosomes (no.21/14) in relation to the history of spontaneous abortion in a family  

PubMed Central

Background: Approximately 205 million pregnancies occur each year in the worldwide. On the other hand, Spontaneous abortion has been reported in 15-20% of all diagnosed pregnancies. The most common cause of spontaneous abortion is chromosomal abnormalities of the embryo. Robertsonian translocation carriers specially 21-14 are the most common balanced rearrangement among the carrier couples with the history of spontaneous abortion. In order to search for balanced chromosomal rearrangement and cytogenetic disorders, 10 members of related family with consanguinity marriage with the history of recurrent miscarriage were assessed. Case: Cytogenetic evaluation on the basis G-banding technique at high resolution was performed in 3 couples and their related family with the history of idiopathic RSA in order to postulate any balanced chromosomal rearrangement. Conclusion: six members of them appeared with robertsonian balanced translocation between chromosome No.21 to No. 14 with the karyotype of 45, XX, t (14, 21) and 45, XY, t (14, 21), which this results are in agreement with several similar works which claimed that the risk of spontaneous abortion in couples with balanced chromosomal rearrangements is higher compared with general population. Considering to results of present study, it seems as if the cytogenetic analysis of couples with the history of recurrent abortions should be suggested compulsory to estimate the probable presence of any chromosomal rearrangement. This offer wills valuable information for genetic consulting. PMID:25408709

Hasanzadeh-NazarAbadi, Mohammad; Baghbani, Fatemeh; Namazi, Iman; Mirzaee, Salmeh

2014-01-01

351

Effects of morphological families on English compound word recognition: A multitask investigation  

Microsoft Academic Search

Three experiments examined the influence of first lexeme morphological family size on English compound word recognition. Concatenated compound words whose first lexemes were from large morphological families were responded to faster in word naming and lexical decision than compounds from small morphological families. In addition, an eye movement experiment showed that gaze durations were shorter on compounds from large morphological

Barbara J. Juhasz; Rachel N. Berkowitz

2011-01-01

352

Datura family: the 2009 update  

NASA Astrophysics Data System (ADS)

Context: Research of asteroid families has been recently refreshed by the discovery of very young ones. These families are of great interest because they represent the product of their parent body fragmentation before orbital and physical evolutionary processes can change them. A cluster of seven objects around the largest body (1270) Datura is of particular interest because it has enough known members and resides in the inner part of the main asteroid belt, facilitating observations. Aims: We carried out photometric observations of the two largest members of the Datura family - asteroids (1270) Datura and (90265) 2003 CL5 - with the goal of inferring their physical parameters. We also used numerous astrometric observations of Datura-family members in the past few years to revisit the age of this cluster. Methods: We performed numerous photometric observations of (1270) Datura over several oppositions. We then used the lightcurve inversion method to determine the spin state and shape of this asteroid. In the case of (90265) 2003 CL5, for which only limited lightcurve data have been acquired so far, we used Fourier analysis to determine the synodic rotation period during the 2008 apparition. We also used backward numerical integration of the improved orbits of Datura family members to reduce uncertainty in its age. Results: We determined the rotation state of (1270) Datura, the largest member of its own family. Its major properties are a short rotation period of ~3.36 h and small obliquity, which, however, exhibits ~±15° excursions because of a forced Cassini state of the proper nodal frequency. Any possible initial non-principal rotation state has probably been damped and the asteroid rotates about the shortest axis of the inertia tensor. Its global shape, although convex in our representation, may reflect regions related to the excavation of the family members from the parent body surface. Interestingly, the second largest member of the Datura family - (90265) 2003 CL5 - appears to be very slow rotator with the rotation period ~24 h. The large amplitude of its rotation curve suggests that its shape is extremely elongated, possibly bi-lobed. Improved orbits of the family members allow us to re-determine the possible age of this family. We find an age that is slightly older than previously reported. Using a conservative approach, we obtain an age in the 450 to 600 kyr range. With strengthened, but plausible, conditions, we find that the current data may support an age of 530±20 kyr. Further astrometric and photometric observations of the Datura cluster members are needed to determine its age more accurately. Photometric data is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/507/495

Vokrouhlický, D.; Durech, J.; Micha?owski, T.; Krugly, Yu. N.; Gaftonyuk, N. M.; Kryszczy?ska, A.; Colas, F.; Lecacheux, J.; Molotov, I.; Slyusarev, I.; Poli?ska, M.; Nesvorný, D.; Beshore, E.

2009-11-01

353

Families, Risk, and Competence.  

ERIC Educational Resources Information Center

The problems of studying families arise from the difficulty in studying systems in which there are multiple elements interacting with each other and with the child. This book attests to the growing sophistication of the conceptualization and measurement techniques for understanding family processes. Chapters in the first part of the book, "The…

Lewis, Michael, Ed.; Feiring, Candice, Ed.

354

Golden Matrix Families  

ERIC Educational Resources Information Center

This student research project explores the properties of a family of matrices of zeros and ones that arises from the study of the diagonal lengths in a regular polygon. There is one family for each n greater than 2. A series of exercises guides the student to discover the eigenvalues and eigenvectors of the matrices, which leads in turn to…

Fontaine, Anne; Hurley, Susan

2011-01-01

355

Family Support and Education  

ERIC Educational Resources Information Center

Family involvement is essential to the developmental outcome of infants born into Neonatal Intensive Care Unit (NICU). In this article, evidence has been presented on the parent's perspective of having an infant in the NICU and the context of family. Key points to an educational assessment are also reviewed. Throughout, the parent's concerns and…

Goldstein, Lou Ann

2013-01-01

356

EATING DISORDERS FAMILY PROBLEMS  

E-print Network

ANXIETY DEPRESSION EATING DISORDERS FAMILY PROBLEMS GENERAL CONCERNS INTERPERSONAL DIFFICULTIES.946.5117 Counselling and Cyber Counselling Services to Help With: · Anxiety · Depression · Eating disorders · Family help. What We Are A new initiative of the Factor-Inwentash Faculty of Social Work, University

Toronto, University of

357

THE URBAN NEGRO FAMILY.  

ERIC Educational Resources Information Center

IN TRACING THE MOVEMENT OF THE NEGRO FAMILY TOWARD A MIDDLE-CLASS ORIENTATION AND TOWARD URBANIZATION, THIS ARTICLE NOTES THAT THE PATTERN IS BECOMING SIMILAR TO THAT OF THE GENERAL AMERICAN FAMILY. NEGROES HAVE LEFT THEIR SOUTHERN RURAL FARMS FOR BOTH SOUTHERN AND NORTHERN URBAN AREAS AND HAVE TENDED TO SETTLE IN THE INNER CORE OF THE LARGEST…

DOUGLASS, JOSEPH H.

358

Understanding Family Interactions  

Microsoft Academic Search

The purpose of this study was to examine the reactions by different family members to various social behaviors by a target child to determine what are the most probable consequences that child will experience. These analyses were based on the home observations of 47 nonclinical families with an identified target child between the ages of four and eight. The probabilities

Linda Musun Baskett

1985-01-01

359

Moving Your Family Overseas.  

ERIC Educational Resources Information Center

This book discusses the challenges that families face in moving overseas. Chapters include: (1) "What This Move Means for Your Family"; (2) "Breaking the News"; (3) "Learning about Your New Country"; (4) "Preparing for the Move"; (5) "The Early Days"; (6) "Culture Shock"; (7) "Expatriate Life"; (8) "How Is Everyone Coping?"; (9) "Social…

Kalb, Rosalind C.; Welch, Penelope

360

Family-Friendly Art  

ERIC Educational Resources Information Center

In the late 1980s, the Denver Art Museum initiated efforts to make the museum a destination for families. From 1997 to 2001, with a generous grant from The Pew Charitable Trusts, these efforts came to fruition. From the moment they walk through the doors, families' needs are anticipated. For example, they can pick up a welcoming brochure, Free…

Williams, Patterson; Garcia, Maria

2004-01-01

361

Workshops on Family Communication.  

ERIC Educational Resources Information Center

Intended to help speech communication professionals become involved in developing, implementing, and evaluating marital or family enrichment programs, this booklet discusses the theory and practice of using marital enrichment programs to increase family harmony. The first section contains an overview of selected enrichment programs, as well as…

Galvin, Kathleen M.

362

Snowbird Intergenerational Family Relationships  

Microsoft Academic Search

This qualitative study examined the family relationships of snowbirds. Interviews were conducted with 25 older adults from the Midwest who migrated seasonally to the Sunbelt. Snowbirds did not perceive their winter experience as having a negative impact on their families in any significant way. The vast majority of snowbirds expressed satisfaction with how well they maintained their intergenerational ties and

Kristine E. Bjelde; Gregory F. Sanders

2009-01-01

363

Changing Families, Changing Workplaces  

ERIC Educational Resources Information Center

American families and workplaces have both changed dramatically over the past half-century. Paid work by women has increased sharply, as has family instability. Education-related inequality in work hours and income has grown. These changes, says Suzanne Bianchi, pose differing work-life issues for parents at different points along the income…

Bianchi, Suzanne M.

2011-01-01

364

WORK FAMILY LIFE !"#"$%&$'()*!("$+(,-./*$"#(.-/,*$/&!&#&0&-/  

E-print Network

, China adopted its strict one-child policy in 1979. 5=F%B9%;=B9%=>GG8EBEH%E--and they feel they can manage this with one child, but not more. Many families would like to have more kids toward one-child families. The U.S. Census Bureau reports that, in the last 20 years, the number

Ginzel, Matthew

365

[Focus: Family Communication].  

ERIC Educational Resources Information Center

This issue of the "Journal of the Wisconsin Communication Association" focuses on family communication and contains the following articles: "Marital Typologies: An Alternative Approach to the Study of Communication in Enduring Relations" by Mary Anne Fitzpatrick, "Intimate Communication and the Family" by Marilyn D. LaCourt, and "A Study in…

Barnes, Richard E., Ed.

1977-01-01

366

Families under Economic Pressure.  

ERIC Educational Resources Information Center

The economic decline of rural America has widespread consequences for families, children, and education. Broad changes in farming and in the rural nonfarm sector have pushed the poverty rate for rural areas in the 1980s higher than the central cities rate. Projections indicate that by the mid-1990s, one-half of all farm families in the midwest may…

Elder, Glen H., Jr.; And Others

367

Explaining Family Interactions.  

ERIC Educational Resources Information Center

A detailed review of current research and state-of-the-art ideas concerning both communication processes and family functioning is presented in this collection of articles. The volume is organized around three sections. Part 1, "The Development of Family Communication Patterns," contains: (1) "Communication in Infancy" (Marguerite Stevenson…

Fitzpatrick, Mary Anne, Ed.; Vangelisti, Anita L., Ed.

368

Family Perspectives on Prematurity  

ERIC Educational Resources Information Center

In this article, seven families describe their experiences giving birth to and raising a premature baby. Their perspectives vary, one from another, and shift over time, depending on each family's circumstances and the baby's developmental course. Experiences discussed include premature labor, medical interventions and the NICU, bringing the baby…

Zero to Three (J), 2003

2003-01-01

369

Education and the Family.  

ERIC Educational Resources Information Center

This book is the report of the Family Ties Commission, which was established by the Association of Teacher Educators to study the relationship between home and school. Following the preface and two introductory essays, "Education and My Family" (K.B. O'Rourke as told to E. Johnson) and "Preparing for Successful Children" (B. Clawson), the book is…

Kaplan, Leonard, Ed.

370

Black Families. Interdisciplinary Perspectives.  

ERIC Educational Resources Information Center

Since the early 1960s, the black family has been characterized as pathological. This six-part collection of 18 research studies presents alternative approaches to understanding the special characteristics of black families. Part I, "Theoretical and Methodological Perspectives," comprises a comparison of the pioneering work of W. E. B. Du Bois and…

Cheatham, Harold E., Ed.; Stewart, James B., Ed.

371

Advancing Measurement of Family Leisure  

E-print Network

of this theory; therefore, 14 anything that happens to one family member will impact all family members. The three prominent and empirically based models of family functioning are: (a) the Beaver’s Family System Model, (b) the Circumplex Model, and (c... Comparison Beaver’s Model of Family Functioning McMaster’s Model of Family Functioning Circumplex Model of Marital and Family Systems Authors Beavers & Hampson Epstein and colleagues Olson & colleagues Year Developed 1977...

Melton, Karen

2014-08-06

372

Marriage And Family Therapy Marriage And Family Therapy  

E-print Network

Marriage And Family Therapy Marriage And Family Therapy Marriage And Family Therapy Thom de Lisa Tedeschi GRADUATE PROGRAM The Department of Marriage and Family Therapy offers an M.A. and a Ph.D. and provides training in marriage and family therapy theory, research, and practice. The faculty seeks

Raina, Ramesh

373

Family planning, AIDS, and FHI.  

PubMed

Family Health International's (FHI) research and development activities in improving and developing contraceptives and making them available to the public are presented. While FHI, along with other agencies, has been actively promoting and contributing to ongoing international family planning efforts since its creation in 1971, the period 1971-91 has, nonetheless, witness more births, maternal deaths, induced abortions, and infant deaths than over any 20-year span in history. While family sizes have decreased over the period due to greater contraceptive awareness and use, politicians, civil servants, and theologians are indicted as partly responsible for retarding further positive change. The number of women of reproductive ages in developing countries will increase by almost 30% in the 1990s, and the world's population will at least double over the next century. 95% of new births will stem from developing countries. Concerted efforts and global commitments of policymakers must be forthcoming in the battle against both high fertility and AIDS prevention. Specifically, at least 130 million new contraceptive users must be recruited in the 1990s. Surveys and field experiences indicate a large degree of unmet need for contraceptive services, with 50-80% of married women in developing countries expressing their desire to limit or space future births. Demand for contraception only increases once a program is in place; rapid reductions of total fertility are exemplified in the cases of Thailand, Colombia, South Korea, Sri Lanka, and Indonesia. Given the resources and commitment, the number of users could be doubled within 10 years. PMID:12284276

Potts, M

1991-09-01

374

Small Family, Smart Family? Family Size and the IQ Scores of Young Men. NBER Working Paper No. 13336  

ERIC Educational Resources Information Center

How do families influence the ability of children? Cognitive skills have been shown to be a strong predictor of educational attainment and future labor market success; as a result, understanding the determinants of cognitive skills can lead to a better understanding of children's long run outcomes. This paper uses a large dataset on the male…

Black, Sandra E.; Devereux, Paul J.; Salvanes, Kjell G.

2007-01-01

375

Family intervention for schizophrenia  

PubMed Central

Background People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. Objectives To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. Search strategy We updated previous searches by searching the Cochrane Schizophrenia Group Trials Register (September 2008). Selection criteria We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. Data collection and analysis We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). Main results This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. Authors’ conclusions Family intervention may reduce the number of relapse events and hospitalisations and would therefore be of interest to people with schizophrenia, clinicians and policy makers. However, the treatment effects of these trials may be overestimated due to the poor methodological quality. Further data from trials that describe the methods of randomisation, test the blindness of the study evaluators, and implement the CONSORT guidelines would enable greater confidence in these findings. PMID:21154340

Pharoah, Fiona; Mari, Jair; Rathbone, John; Wong, Winson

2014-01-01

376

Large intestine  

NSDL National Science Digital Library

The large intestine is larger and shorter than the small intestine and connects to the small intestine and the anus. Nutrient deficient material from the small intestine travels through the large intestine to the anus. This material is called feces and is excreted. Feces is made up of material that our bodies cannot break down into smaller parts to be used by the body.

Katie Hale (CSUF; )

2007-08-18

377

Family Structure and Social Influence.  

ERIC Educational Resources Information Center

Regardless of family form, there is a universal belief that one's family is the most powerful agent of socialization. A sample of 38 junior high school students from single parent and nuclear families completed a questionnaire in order to examine the relative effects of peer influence and family influence in single parent and nuclear families.…

Olson, Dawn R.

378

Does Addiction Run in Families?  

MedlinePLUS

Listen to this page Does Addiction Run in Families? Addiction can run in families. If people in your family have addictions, you are more likely to become ... En español "Heart disease runs in some families. Addiction runs in ours." Matt's family has a history ...

379

Help Your Family Face Challenges Successfully: Building Your Family's Resilience  

MedlinePLUS

... how!. Apply Now Home » Resilience: Total Force Fitness Help Your Family Face Challenges Successfully: Building Your Family's ... own and your family's resilience, this information may help. What is resilience? One popular definition of resilience ...

380

Family Emergency Preparedness Plan 1 Family Emergency Preparedness Plan  

E-print Network

#12;#12;Family Emergency Preparedness Plan 1 Family Emergency Preparedness Plan Why Plan.....................................................................21 Hazardous Material Accidents ..............................................22 Nuclear Power Plants Emergency Telephone Numbers.....................................................26 Credits The Family

Noble, James S.

381

75 FR 9247 - Single Family Mortgage Insurance Premium, Single Family  

Federal Register 2010, 2011, 2012, 2013

...DEVELOPMENT [Docket No. FR-5376-N-13] Single Family Mortgage Insurance Premium, Single Family AGENCY: Office of the Chief Information Officer...the subject proposal. Lenders use the Single Family Premium Collection Subsystem-Upfront...

2010-03-01

382

Partners in family planning.  

PubMed

Studies of the Africa OR/TA Project and other Cooperating Agencies suggest that support of family planning by traditional health practitioners (THPs), traditional birth attendants (TBAs), Islamic religious leaders, and male opinion leaders (MOLs) can result in an increase in the availability of family planning services in the community. A study in Kenya shows that 100 trained THPs who were actively involved in family planning (i.e., distributors of condoms, oral contraceptives, and primary health care drugs) increased contraceptive use in Siaya and Kakamega districts from 7% to 15% and from 14% to 34%, respectively. Contraceptive use did not change in the 2 control areas. Two years after TBAs underwent training in family planning promotion, the proportion of women who named TBAs as their source of family planning information increased from 2% to 18%. In The Gambia, integration of Islamic religious leaders into family planning promotion activities resulted in an increase of current modern contraceptive method use from 9% to 20% for males and from 9% to 26% for females. Involvement of 69 MOLs has increased knowledge of family planning methods in Nkambe, Cameroon. For example, among males, knowledge about the condom increased from 52% to 81% and knowledge about spermicides increased from 12% to 44%. The corresponding figures for women were 47% to 72% and 17% to 42%, respectively. PMID:12319039

1994-12-01

383

A family quarrel? "Developmentalism" or family planning.  

PubMed

The switch in emphasis in population policies from family planning to the development of socioeconomic policies that would encourage smaller families--summed up in the word "developmentalism"--is charted from a 1967 paper by Kinsley Davis to its culmination at the 1974 World Population Conference, when even as staunch a supporter of family planning as John D. Rockefeller came out in support of placing population policy in the context of economic and social development. The real question is, however: To what extent does developmentalism represent a true shift in policy and how much is simply a more sophisticated rhetoric designed to deflect the growing opposition to population control? On the one hand, the endorsement by a man of Rockefeller's stature indicates a significant change. On the other, the changes which the implementation of developmentalism would entail seem irreconcilable with the present political and economic structures of underdeveloped nations and of relations between them and the more developed countries. Further, developmentalism is neither as progressive as its advocates suggest, nor as threatening as its opponents cry. It is, in fact, a prescription for enhancing the effectiveness of family planning through a form of social engineering from the top; its details--more aid, investment, and trade--would involve an expanded Western role in the Third World. It is even suggested that developmentalism might be a cover for the creation of a more stratified society, where marginal members are restricted to their own quarters in an effort to secure political stability and economic growth. In the end, developmentalism might be shortlived, as pressure to step up birth control programs is felt from many quarters. PMID:12307032

Carder, M

1974-01-01

384

Familial Aggregation of Autoimmune Disease in Juvenile Dermatomyositis  

PubMed Central

OBJECTIVE: Familial aggregation of autoimmune diseases likely reflects shared pathogenic factors between different diseases. Familial aggregation of autoimmunity has not been examined in juvenile dermatomyositis. Interferon-? is thought to be a pathogenic factor in both systemic lupus erythematosus and juvenile dermatomyositis, and we have previously demonstrated familial aggregation of serum interferon-?. METHODS: Family histories were obtained from 304 families of children with juvenile dermatomyositis via 3-generation structured interviews performed by the same person. Rates of autoimmune disease in families of children with juvenile dermatomyositis were compared with published population rates. Serum interferon-?, tumor necrosis factor-?, and neopterin were measured using standard techniques. RESULTS: A total of 51% of families of children with juvenile dermatomyositis reported at least 1 additional member affected by an autoimmune disease. In particular, both type 1 diabetes and systemic lupus erythematosus were significantly more common than would be expected (odds ratio >5, P ? 1 × 10?7 for both). Pedigree analysis showed particularly strong familial clustering of systemic lupus erythematosus with little decrease in incidence across generations, suggesting the possibility of rare causal genes with large effect. Untreated subjects with juvenile dermatomyositis with a family history of systemic lupus erythematosus had higher serum interferon-? than those who did not (P = .047). CONCLUSIONS: We find strong familial aggregation of specific autoimmune diseases in families of children with juvenile dermatomyositis, suggesting that these conditions share pathogenic factors. Higher serum interferon-? in juvenile dermatomyositis patients with a family history of systemic lupus erythematosus suggesting that interferon-? is one such shared factor. PMID:21502224

Wu, Stephanie C.; Smith, Molly; Morgan, Gabrielle A.; Pachman, Lauren M.

2011-01-01

385

Gene Family Evolution across 12 Drosophila Genomes  

Microsoft Academic Search

Comparison of whole genomes has revealed large and frequent changes in the size of gene families. These changes occur because of high rates of both gene gain (via duplication) and loss (via deletion or pseudogenization), as well as the evolution of entirely new genes. Here we use the genomes of 12 fully sequenced Drosophila species to study the gain and

Matthew W Hahn; Mira V Han; Sang-Gook Han

2007-01-01

386

Homozygosity mapping reveals new nonsense mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in a Palestinian family  

PubMed Central

Purpose: Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 45 genes. Recently, the FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. Methods: We performed a clinical and molecular genetic study of a consanguineous Palestinian family with two three siblings affected with retinitis pigmentosa. DNA samples were collected from the index patient, his father, his affected sister, and two non-affected brothers. DNA sample from the index was subjected to high resolution genome-wide SNP array. Assuming identity-by-descent in this consanguineous family we applied homozygosity mapping to identify disease causing genes. Results: The index patient reported night blindness since the age of 20 years, followed by moderate disease progression with decrease of peripheral vision, the development of photophobia and later on reduced central vision. At the age of 40 his visual acuity was counting fingers (CF) for both eyes, color discrimination was not possible and his visual fields were severely constricted. Funduscopic examination revealed a typical appearance of advanced RP with optic disc pallor, narrowed retinal vessels, bone-spicule like pigmentary changes in the mid-periphery and atrophic changes in the macula. His younger affected brother (37 years) was reported with overall milder symptoms, while the youngest sister (21 years) reported problems only with night vision. Applying high-density SNP arrays we identified several homozygous genomic regions one of which included the recently identified FAM161A gene mutated in RP28-linked autosomal recessive RP. Sequencing analysis revealed the presence of a novel homozygous nonsense mutation, c.1003C>T/p.R335X in the index patient and the affected sister. Conclusion: We identified an RP28-linked RP family in the Palestinian population caused by a novel nonsense mutation in FAM161A. RP in this family shows a typical disease onset with moderate to rapid progression into severe visual impairment including central vision in the index and overall milder symptoms in the younger brother and sister. PMID:24520187

Zobor, Ditta; Balousha, Ghassan; Baumann, Britta

2014-01-01

387

Predictors of Family Structure  

NSDL National Science Digital Library

This activity is used in an sociology class class for undergraduate students. This activity explores topics of households/families, income and race to understand how family structure and demographic information predict trends in family structure. This activity uses a customized data set made from combining census information from 1950-1990 and guides students through data manipulation using WebCHIP software found at DataCounts!. To open WebCHIP with the dataset for the activity, please see instructions and links in the exercise documents under teaching materials. For more information on how to use WebCHIP, see the How To section on DataCounts!

Maxine Atkinson

388

A family of strangers  

E-print Network

invo'Ived. 3. Wife's desires regarding employment, regardless of other considerations in the union. 4. Stress as it relates to the husband because he feels the need for total or major responsibility for financial solvency. 5. Stress as it relates... source of family income. 3. If the wife views her husband's occupation as the primary source of family income, she will view her potential or actual occupation as a secondary source of family income. 4. If the couple has consensus on male-female roles...

Sonnenfeld, Carol Price

1975-01-01

389

Evolutionary families of peptidases.  

PubMed Central

The available amino acid sequences of peptidases have been examined, and the enzymes have been allocated to evolutionary families. Some of the families can be grouped together in 'clans' that show signs of distant relationship, but nevertheless, it appears that there may be as many as 60 evolutionary lines of peptidases with separate origins. Some of these contain members with quite diverse peptidase activities, and yet there are some striking examples of convergence. We suggest that the classification by families could be used as an extension of the current classification by catalytic type. PMID:8439290

Rawlings, N D; Barrett, A J

1993-01-01

390

Stigmatization of Non-Normative Family Size Status  

Microsoft Academic Search

Prior person perception studies exposednormative expectations about family size such thatvoluntary childfree and single-child women werestigmatized and large-family mothers were glorified. Incontrast, self-reports find no differences in subjectivewell-being among these non-normative and 2 to 3 child,normative women. To explore mostly white,college-educated, employed women's experiences withtheir real-life family size choices, interviews wereconducted with 15 voluntary childfree, 15 one-child, and15 supernormative mothers

Karla A. Mueller; Janice D. Yoder

1999-01-01

391

The potential impact of family history of metabolic syndrome and risk of type 2 diabetes mellitus: In a highly endogamous population  

PubMed Central

Aim: This study aims to determine the potential impact of positive family history of Metabolic Syndrome (MetS) among two generations, on developing Type 2 Diabetes Mellitus (T2DM) and the potential relation of consanguineous marriage among patients with MetS to the risk of developing T2DM among a sample of Qataris. Design: A cross-sectional study. Setting: Primary healthcare (PHC) centers. Materials and Methods: The survey and measurement were conducted from April 2011 to December 2012 among Qatari nationals above 20 years of age. Of the 2,182 subjects, who were approached to participate in the study, 1,552 (71%) gave their consent. Face-to-face interviews were conducted using a structured questionnaire followed by anthropometric measurements and laboratory tests. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (ATP III) as well as International Diabetes Federation (IDF). Results: Overall, the prevalence of MetS was 26.2% according to ATP III and 36.9% according to IDF (P < 0.0001). The mean age of MetS patients with T2DM was significantly higher than those without T2DM (Mean 48 ± 9.9 vs. 42.5 ± 9.2; P < 0.001). The proportion of females was higher among MetS patients with T2DM as compared to those without T2DM (61% vs. 51%; P = 0.053). In addition, there were significant differences between MetS patients with and without DM in terms of co-morbidities of hypertension, coronary heart disease, and high cholesterol. The proportion of MetS patients with positive family history for MetS was significantly higher in MetS patients with T2DM as compared to those without T2DM (46.7% vs. 33.8%; P = 0.009). The proportion of positive family history of MetS among fathers (35% vs. 21.9%; P = 0.005), mothers (30.5% vs. 18.8%; P = 0.008), maternal aunt (18.3% vs. 11.2%; P = 0.055), and maternal grand father (19.5% vs. 10%; P = 0.010) were significantly higher in MetS patients with T2DM as compared to the counterpart. The proportion of consanguineous marriages was almost two times higher among MetS patients with T2DM as compared to those without T2DM (80.9% vs. 41.9%; P < 0.001). The proportion of MetS patients with T2DM was lower than MetS patients without DM below 45 years, but after 45 years, the proportion of MetS patients with T2DM remained higher than their counterparts. Conclusion: Family history of MetS among parents, maternal aunt, maternal grandfather, and consanguineous marriages among patients of MetS are significantly associated with the development of T2DM in Qatar. These results support the necessity of earlier screening for T2DM among MetS patients with positive family history of MetS. PMID:24741517

Bener, Abdulbari; Darwish, Sarah; Al-Hamaq, Abdulla O. A.; Yousafzai, Mohammad T.; Nasralla, Eman A.

2014-01-01

392

Family Demands, Social Support and Family Functioning in Taiwanese Families Rearing Children with Down Syndrome  

ERIC Educational Resources Information Center

Background: Down syndrome (DS) affects not only children but also their families. Much remains to be learned about factors that influence how families of children with DS function, especially families in non-Western populations. The purpose of this cross-sectional, correlational study was to examine how family demographics, family demands and…

Hsiao, C-Y.

2014-01-01

393

Familial Poverty, Family Allowances, and the Normative Family Structure in Britain, 1917-1945  

Microsoft Academic Search

In 1945, the Family Allowances Act was incorporated into law. The family allowances scheme depended on the maintenance of a normative family structure and a wage system that discriminated against women. Eleanor Rathbone, along with social surveyors of the 1930s and social policy makers, recognized the family wage system as a primary cause of poverty among working families. Unfortunately, the

Colleen Margaret Forrest

2001-01-01

394

Family Therapy, Family Practice, and Child and Family Poverty: Historical Perspectives and Recent Developments  

ERIC Educational Resources Information Center

This paper assesses the engagement of family therapy and family practice with families with children, who are living in poverty. It analyzes four promising models from two perspectives. The first perspective relates to critiques, which have been made of the practice of family therapy with families living in poverty; and the second relates to the…

Frankel, Harvy; Frankel, Sid

2006-01-01

395

Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer  

PubMed Central

Background Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes. PMID:24723567

Andersson, Ulrika; Wibom, Carl; Cederquist, Kristina; Aradottir, Steina; Borg, Åke; Armstrong, Georgina N.; Shete, Sanjay; Lau, Ching C.; Bainbridge, Matthew N.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Lai, Rose; Il'yasova, Dora; Houlston, Richard S.; Schildkraut, Joellen; Bernstein, Jonine L.; Olson, Sara H.; Jenkins, Robert B.; Lachance, Daniel H.; Wrensch, Margaret; Davis, Faith G.; Merrell, Ryan; Johansen, Christoffer; Sadetzki, Siegal; Bondy, Melissa L.; Melin, Beatrice S.; Adatto, Phyllis; Morice, Fabian; Payen, Sam; McQuinn, Lacey; McGaha, Rebecca; Guerra, Sandra; Paith, Leslie; Roth, Katherine; Zeng, Dong; Zhang, Hui; Yung, Alfred; Aldape, Kenneth; Gilbert, Mark; Weinberger, Jeffrey; Colman, Howard; Conrad, Charles; de Groot, John; Forman, Arthur; Groves, Morris; Levin, Victor; Loghin, Monica; Puduvalli, Vinay; Sawaya, Raymond; Heimberger, Amy; Lang, Frederick; Levine, Nicholas; Tolentino, Lori; Saunders, Kate; Thach, Thu-Trang; Iacono, Donna Dello; Sloan, Andrew; Gerson, Stanton; Selman, Warren; Bambakidis, Nicholas; Hart, David; Miller, Jonathan; Hoffer, Alan; Cohen, Mark; Rogers, Lisa; Nock, Charles J; Wolinsky, Yingli; Devine, Karen; Fulop, Jordonna; Barrett, Wendi; Shimmel, Kristen; Ostrom, Quinn; Barnett, Gene; Rosenfeld, Steven; Vogelbaum, Michael; Weil, Robert; Ahluwalia, Manmeet; Peereboom, David; Staugaitis, Susan; Schilero, Cathy; Brewer, Cathy; Smolenski, Kathy; McGraw, Mary; Naska, Theresa; Rosenfeld, Steven; Ram, Zvi; Blumenthal, Deborah T.; Bokstein, Felix; Umansky, Felix; Zaaroor, Menashe; Cohen, Avi; Tzuk-Shina, Tzeela; Voldby, Bo; Laursen, René; Andersen, Claus; Brennum, Jannick; Henriksen, Matilde Bille; Marzouk, Maya; Davis, Mary Elizabeth; Boland, Eamon; Smith, Marcel; Eze, Ogechukwu; Way, Mahalia; Lada, Pat; Miedzianowski, Nancy; Frechette, Michelle; Paleologos, Nina; Byström, Gudrun; Svedberg, Eva; Huggert, Sara; Kimdal, Mikael; Sandström, Monica; Brännström, Nikolina; Hayat, Amina; Tihan, Tarik; Zheng, Shichun; Berger, Mitchel; Butowski, Nicholas; Chang, Susan; Clarke, Jennifer; Prados, Michael; Rice, Terri; Sison, Jeannette; Kivett, Valerie; Duo, Xiaoqin; Hansen, Helen; Hsuang, George; Lamela, Rosito; Ramos, Christian; Patoka, Joe; Wagenman, Katherine; Zhou, Mi; Klein, Adam; McGee, Nora; Pfefferle, Jon; Wilson, Callie; Morris, Pagan; Hughes, Mary; Britt-Williams, Marlin; Foft, Jessica; Madsen, Julia; Polony, Csaba; McCarthy, Bridget; Zahora, Candice; Villano, John; Engelhard, Herbert; Borg, Ake; Chanock, Stephen K; Collins, Peter; Elston, Robert; Kleihues, Paul; Kruchko, Carol; Petersen, Gloria; Plon, Sharon; Thompson, Patricia; Johansen, C.; Sadetzki, S.; Melin, B.; Bondy, Melissa L.; Lau, Ching C.; Scheurer, Michael E.; Armstrong, Georgina N.; Liu, Yanhong; Shete, Sanjay; Yu, Robert K.; Aldape, Kenneth D.; Gilbert, Mark R.; Weinberg, Jeffrey; Houlston, Richard S.; Hosking, Fay J.; Robertson, Lindsay; Papaemmanuil, Elli; Claus, Elizabeth B.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Sloan, Andrew E.; Barnett, Gene; Devine, Karen; Wolinsky, Yingli; Lai, Rose; McKean-Cowdin, Roberta; Il'yasova, Dora; Schildkraut, Joellen; Sadetzki, Siegal; Yechezkel, Galit Hirsh; Bruchim, Revital Bar-Sade; Aslanov, Lili; Sadetzki, Siegal; Johansen, Christoffer; Kosteljanetz, Michael; Broholm, Helle; Bernstein, Jonine L.; Olson, Sara H.; Schubert, Erica; DeAngelis, Lisa; Jenkins, Robert B.; Yang, Ping; Rynearson, Amanda; Andersson, Ulrika; Wibom, Carl; Henriksson, Roger; Melin, Beatrice S.; Cederquist, Kristina; Aradottir, Steina; Borg, Åke; Merrell, Ryan; Lada, Patricia; Wrensch, Margaret; Wiencke, John; Wiemels, Joe; McCoy, Lucie; McCarthy, Bridget J.; Davis, Faith G.

2014-01-01

396

National Military Family Association  

MedlinePLUS

... Military Families in 2014. Apply for Military Spouse Scholarships We want to help military spouses gain meaningful ... the ways we do this is by offering scholarships to spouses of all Uniformed Services. Apply Now! ...

397

Familial Mediterranean fever  

MedlinePLUS

... Recurrent polyserositis; Benign paroxysmal peritonitis; Periodic disease; Periodic fever; FMF ... Familial Mediterranean fever is most often caused by a mutation in the MEFV gene. This gene creates proteins involved in inflammation. ...

398

Normal Functioning Family  

MedlinePLUS

... love and caring for other family members; providing security and a sense of belonging; open communication; making ... Academy of Pediatrics) The information contained on this Web site should not be used as a substitute ...

399

Family in Crisis  

MedlinePLUS

... safe. Don't take away that sense of security they're constructing for themselves. Older children & adolescents ... again) can help increase your family's sense of security. Find ways to help others Finally, provide your ...

400

Family Reunion Health Guide  

MedlinePLUS

... and on the Phone 17 Share Materials 20 Planning Tips NATIONAL KIDNEY DISEASE EDUCATION PROGRAM l FAMILY ... with you. Contact these organizations early in your planning process to make arrangements. 5 of 23 CONTENTS ...

401

Family Decision Making  

MedlinePLUS

... Makers Error processing SSI file Family Decision Making Language: English Español (Spanish) Share Compartir Communicating How can I ... Blood Disorders & Disabilities Information For... Media Policy Makers Language: English Español (Spanish) File Formats Help: How do I ...

402

Care of the Family  

MedlinePLUS

... one) is a natural, anticipated process after death. Palliative care provides support to family members preparing for the ... This website is funded by your generous support. Care to Donate ? ©2000-2011 Continuum Health Partners, Inc.

403

My Fact Family  

NSDL National Science Digital Library

Students will use cut out people shapes and number cards to create two addition problems and two subtraction problems using the same three numbers of a fact family to explore the commutative property.

Gehron, Elizabeth

2012-08-15

404

Technology and the Family.  

ERIC Educational Resources Information Center

Technology affects family life, size, structure, and relationships and blurs distinctions between home and work. It is imperative to keep sight of human values and a human agenda and to insist that technology serve people, not drive policy. (SK)

McTeer, Maureen A.

1995-01-01

405

Teaching Family Medicine  

PubMed Central

Students should study the family system just as they would an organ system, making use of family studies and home visits. A comparison of private and academic faculty revealed the need to instruct private practitioners on patient selection and teaching methodology. Experience has shown that patients from the lower socioeconomic classes tend to allow the student to participate more in their family life and health care and that, in return, the student is often able to assist these patients in some way. Faculty must guide, monitor, and assist students with problems. Audit of students' and patients' reports on and evaluations of the family study will provide valuable information for planning future programs or revamping continuing ones. PMID:21308094

Baumslag, Naomi

1976-01-01

406

job families EXPLORATION  

E-print Network

of computer systems. BUSINESS DEVELOPMENT Workers in this job group engage in the preparation, negotiationjob families EXPLORATION JOB GROUPS EXAMPLE OCCUPATIONS getgrowing CAREER PATHS WWW Bioinformatics professionals build the technological tools that are needed to improve the data analysis process

Muzzio, Fernando J.

407

[Family violence and generations].  

PubMed

Starting with a description of the place and function of violence inside families, the author raises than the topics of the professional's ethic and responsibility when working with family violence. It is not always easy for professionals to evaluate responsibilities particularly when they try to take into account as many contextual factors as possible. They could worry to become too Manichean and to see themselves as following only a linear causality. PMID:21089424

Goldbeter-Merinfeld, E

2010-09-01

408

Building Family Capacity for Native Hawaiian Women with Breast Cancer  

ERIC Educational Resources Information Center

Native Hawaiian women have the highest breast cancer incidence and mortality rates when compared with other large ethnic groups in Hawai'i. Like other women, they rely on the support of their families as co-survivors. This project explored the feasibility and effects of a culturally tailored educational intervention designed to build family

Mokuau, Noreen; Braun, Kathryn L.; Daniggelis, Ephrosine

2012-01-01

409

Work—Family Facilitation: Expanding Theoretical Understanding Through Qualitative Exploration  

Microsoft Academic Search

The problem and the solution. Work—family scholarly research is often dominated by a conflict perspective. In this study, employees of a large multinational corporation were asked to describe the positive influences of their work life on their home life and vice versa. Participants most frequently mentioned work place flexibility, financial benefits, and the ability to keep family commitments as important

E. Jeffrey Hill; Sarah Allen; Jenet Jacob; Ashley Ferrin Bair; Sacha Leah Bikhazi; Alisa Van Langeveld; Giuseppe Martinengo; Taralyn Trost Parker; Eric Walker

2007-01-01

410

Intergenerational Family Solidarity: Value Differences Between Immigrant Groups and Generations  

Microsoft Academic Search

Although immigrants may be more dependent on their immediate family for support, they may also experience a wider generation-gap in values regarding intergenerational solidarity, because of processes of acculturation. Based on large scale survey data (N = 2,028), differences between first and second generation immigrants in values regarding intergenerational solidarity were examined among family members in the Netherlands with an

Eva-Maria Merz; Ezgi Özeke-Kocabas; Frans J. Oort; Carlo Schuengel

2009-01-01

411

The Peale Family Papers  

NSDL National Science Digital Library

Housed at the Smithsonian Institution's National Portrait Gallery, The Charles Willson Peale Family Papers is a boon to researchers in the history and culture of America from the 1730s to the 1880s. Comprised of copies of more than 6,000 documents, spanning three generations of the Peale family, "the archive traces the family's history from the arrival of Charles Peale, a transported felon, through the career of Charles Willson Peale -- artist, Revolutionary soldier, naturalist and museum keeper, and Enlightenment polymath -- down through the nineteenth-century careers and lives of his many children." Unfortunately, the papers themselves are not accessible online, but the site features essays discussing the papers, the history of the Peale family, and the editorial philosophy behind the publication of the first four volumes of the Peale Family Papers. (The entire collection is currently available in microfiche, and bibliographic information about this resource and the print publications of the papers are provided on-site.) The Website also features a photo gallery of paintings either by or of Peale family members.

412

Brassicaceae (Mustard family) Field pennycress  

E-print Network

Brassicaceae (Mustard family) Field pennycress Thlaspi arvense L. Life cycle Erect winter or summer. Back to identifying Christmas tree weeds. #12;Brassicaceae (Mustard family) Field pennycress continued

413

Brassicaceae (Mustard family) Hoary alyssum  

E-print Network

Brassicaceae (Mustard family) Hoary alyssum Berteroa incana (L.) DC. Life cycle Annual, biennial to identifying Christmas tree weeds. #12;Brassicaceae (Mustard family) oval and slightly flattened, grayish green

414

Family planning and the Malawian male.  

PubMed

To curb the deleterious socioeconomic effects of rapid population growth, the Government of Malawi has adopted a National Child Spacing Program. Women who attend maternal health centers are counseled about the harmful effects of closely spaced childbearing, informed of contraceptive options, and urged to discuss family planning with their husband. This strategy fails to consider the control by Malawian men over women's reproductive capacities and family size decision making. If Malawi's child spacing program is to be successful in reducing fertility, the emphasis must be shifted to men. Needed is an educational campaign to convince men that large family size--currently considered a sign of virility--adversely affects the family's standard of living. Malawian men are more likely to be convinced by arguments based on economics than concerns about maternal-child health. For example, educational messages could focus on the inability of malnourished children to perform farm work, the higher incomes and ability to provide old age support of well-educated children, the high price of a large dwelling, and the debts incurred by providing food and clothing for many children. Specific target groups in need of such interventions include low-income skilled and semi-skilled urban workers, smallholder farmers, and small-scale businessmen. In rural areas, family planning messages can be incorporated into existing agricultural extension and functional literacy programs. PMID:12319396

Kishindo, P

1994-01-01

415

Whole-exome sequencing diagnosis of two autosomal recessive disorders in one family.  

PubMed

Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous disorder for which sub-typing through molecular analysis can help determine the eventual phenotype and prognosis. We used whole-exome sequencing to identify a new homozygous splice site mutation in ST14 (IVS5+1G>A), encoding matriptase, in a 4-year-old girl with ARCI from a consanguineous Kuwaiti family. Clinically, she also had hypotrichosis, which supported a diagnosis of ARCI11. Only 4 previous examples of pathogenic mutations in ST14 have been reported and the findings expand genotype-phenotype correlation for this subtype of ARCI. Our patient was the second child born to these parents: the first (deceased) and third children had congenital brain and eye abnormalities, of uncertain aetiology and with no precise diagnosis. Further analysis of our ARCI11 patient's exome dataset revealed heterozygosity for a splice site mutation in POMT1 (IVS4+1G>T), encoding protein O-mannosyltransferase, a gene implicated in Walker-Warburg syndrome. DNA sequencing in the third child showed homozygosity for this mutation in POMT1. The first cousin parents were both heterozygous for the splice site mutations in ST14 and POMT1. In this family, whole-exome sequencing was able to accurately subtype a form of ARCI in one child and provide an explanation for an undiagnosed developmental disorder in two other children, findings that improve diagnostic accuracy and genetic counselling, and demonstrate the impact of next generation sequencing technologies on clinical genetics. This article is protected by copyright. All rights reserved. PMID:25308318

Takeichi, T; Nanda, A; Aristodemou, S; McMillan, J R; Lee, J; Akiyama, M; Al-Ajmi, H; Simpson, M A; McGrath, J A

2014-10-11

416

[Mutation analysis of the pathogenic gene in a Chinese family with hereditary hemochromatosis].  

PubMed

Hereditary hemochromatosis (HHC) is a rare autosomal recessive disorder. We recruited a consanguineous Chinese family including the proband with HHC and other four members without HHC. Using whole-exome sequencing, we identified two homozygous mutations (c.G18C [p.Q6H] and c.GC962_963AA [p.C321X]) in the hemojuvelin gene (HJV) in the proband with HHC. No mutation was found in other four previously identified HHC related genes, HAMP, TFR2, FPN and HFE. The functional impact of p.Q6H mutation is weak whereas p.C321X, a premature termination mutation, results in a truncated HJV protein, which lacks the glycosylphosphatidylinositol (GPI) anchor domain. In addition to the mutations in HJV, other 12 homozygous mutations were identified in this patient. However, none of these mutations showed strong damaging impact and the mutated genes are not related to iron metabolism. Our in-house data further demonstrated that p.C321X is absent in the general Chinese population, suggesting that the homozygous mutation p.C321X in HJV is causative in the patient with HHC. Accordingly, all of the four members without HHC from the same family carried wild-type alleles or heterozygous mutations, but not the homozygous mutation in this site. Thus, we found for the first time that the homozygous mutation p.C321X in HJV can result in HHC, which will help genetic diagnosis and prenatal counseling for HHC. PMID:25567873

Yuanfeng, Li; Hongxing, Zhang; Haitao, Zhang; Xiaobo, Peng; Lili, Bai; Fuchu, He; Zewu, Qiu; Gangqiao, Zhou

2014-11-01

417

Exome sequencing identifies a novel homozygous variant in NDRG4 in a family with infantile myofibromatosis.  

PubMed

Infantile myofibromatosis (IM) is a rare disorder characterized by the development of benign tumors in the skin, muscle, bone, and viscera. The incidence is 1/150,000 live births and the disease is the most common cause of fibrous tumors in infancy. Cases which lack visceral involvement generally have a more benign course, usually with spontaneous regression of the tumors. On the other hand, the prognosis tends to be unfavorable when there is involvement of vital organs, which can lead to significant mortality. The identification of rare variants in genes that may cause IM is the first step towards the possibility of targeted treatments; however, the molecular pathogenesis of IM is poorly understood. In the present study, we report the results of exome sequence analysis of two brothers diagnosed with visceral multicentric infantile myofibromatosis, and their healthy consanguineous parents. In the two brothers we identified novel homozygous variants in NDRG4 gene (N-myc downregulated gene family member 4) and in RLTPR gene (RGD motif, leucine rich repeats, tropomodulin domain and proline-rich containing). The healthy parents were heterozygous for both variants. Consistent with the phenotype of IM, NDRG4 is a tumor-related gene; its expression has been shown to be decreased in numerous tumor types, suggesting that it might be a tumor suppressor gene. Additionally, studies have demonstrated that NDRG4 may have a role in cell survival and tumor invasion. We thus propose that this homozygous variant in NDRG4 may be the causative variant of the autosomal recessive form of IM in the studied family and that it should be investigated in other cases of autosomal recessive infantile myofibromatosis. PMID:25241110

Linhares, Natália D; Freire, Maíra C M; Cardenas, Raony G C C L; Pena, Heloísa B; Bahia, Magda; Pena, Sergio D J

2014-01-01

418

Changing families, changing workplaces.  

PubMed

American families and workplaces have both changed dramatically over the past half-century. Paid work by women has increased sharply, as has family instability. Education-related inequality in work hours and income has grown. These changes, says Suzanne Bianchi, pose differing work-life issues for parents at different points along the income distribution. Between 1975 and 2009, the labor force rate of mothers with children under age eighteen increased from 47.4 percent to 71.6 percent. Mothers today also return to work much sooner after the birth of a child than did mothers half a century ago. High divorce rates and a sharp rise in the share of births to unmarried mothers mean that more children are being raised by a single parent, usually their mother. Workplaces too have changed, observes Bianchi. Today's employees increasingly work nonstandard hours. The well-being of highly skilled workers and less-skilled workers has been diverging. For the former, work hours may be long, but income has soared. For lower-skill workers, the lack of "good jobs" disconnects fathers from family obligations. Men who cannot find work or have low earnings potential are much less likely to marry. For low-income women, many of whom are single parents, the work-family dilemma is how to care adequately for children and work enough hours to support them financially. Jobs for working-class and lower middle-class workers are relatively stable, except in economic downturns, but pay is low, and both parents must work full time to make ends meet. Family income is too high to qualify for government subsidized child care, but too low to afford high-quality care in the private market. These families struggle to have a reasonable family life and provide for their family's economic well-being. Bianchi concludes that the "work and family" problem has no one solution because it is not one problem. Some workers need more work and more money. Some need to take time off around the birth of a child without permanently derailing a fulfilling career. Others need short-term support to attend to a family health crisis. How best to meet this multiplicity of needs is the challenge of the coming decade. PMID:22013627

Bianchi, Suzanne M

2011-01-01

419

Family ownership and firm performance: Influence of family management, family control, and firm size  

Microsoft Academic Search

This study examines the relationship between family ownership and firm performance by considering the influence of family\\u000a management, family control, and firm size. Using proxy data of 786 public family firms in Taiwan during 2002–2007, this study\\u000a found that family ownership is positively associated with firm performance. The positive association is strong particularly\\u000a when family members serve as CEOs, top

Wenyi Chu

2011-01-01

420

[Natural family planning].  

PubMed

Natural family planning (NFP) is based on the knowledge *largely nonexistent) of a women as to whether she is in her fertile period or not. In contrast to the calendar method, the Billings method consists of observing bodily functions, whereby women learn about the fertile and infertile period during the menstrual cycle. This method is very safe as long as the woman has been instructed thoroughly. The Pearl index (the number of pregnancies/100 woman years) can be 1. In a Swedish province, 7/1000 population used this method and had an abortion rate of .5/1000, a fact contradicting the allegation of mass abortion as a result of the method. Only well-trained NFP instructors can teach women, and at the University of Umea such training has been available for some years. The biological basis of the Billings method rests on the fact that every release of an egg is preceded by a ripening process of a follicle in the ovary. This follicle secretes increasing amounts of estrogen which stimulates the cervix to produce secretions for the sperm. Right before ovulation, the follicle reduces estrogen production and noradrenaline takes over, stimulating the peak-day secretion (P-secretion) for further selection of sperm. Ovulation usually occurs on the peak day, which is the day of maximum fertility and the last day of mucous symptoms. For 3 days after peak day until menstruation, the risk of becoming pregnant diminishes successively until it is as low as after sterilization. The instructor is trained to recognize and overcome certain factors that make it more difficult to identify the mucous symptoms, such as the previous use of oral contraceptives, certain illnesses, drugs, and life styles. NFP can also be used for attaining pregnancy by identifying the peak day; women with premenstrual syndrome can calculate when their symptoms start, and sportswomen can predict the time of their menstruation. NFP is fascinating when it is compared to other methods because of its human dimension, and there is still a great deal to be learned about it. PMID:1618690

Odeblad, E

1992-06-01

421

Marriage And Family Therapy Marriage And Family Therapy  

E-print Network

Marriage And Family Therapy Marriage And Family Therapy Thom deLara, Chair, 315-443-9830 Peck Hall-443-3024 The Department of Marriage and Family Therapy offers an M.A. and a Ph.D. and provides training in marriage of the practice and profession of marriage and family therapy through scholarly research, education, training

Mather, Patrick T.

422

Marriage And Family Therapy Marriage And Family Therapy  

E-print Network

Marriage And Family Therapy Marriage And Family Therapy Thom deLara, Chair, 315-443-9830 1045 James Supervisor T. Reichert-Schimpff GRADUATE PROGRAM The Department of Marriage and Family Therapy offers an M.A. and a Ph.D. and provides training in marriage and family therapy theory, research, and practice

McConnell, Terry

423

Marriage And Family Therapy Marriage And Family Therapy  

E-print Network

Marriage And Family Therapy Marriage And Family Therapy Thom deLara, Chair, 315-443-9830 1045 James Linda Stone Fish, Graduate Program Director, 315-443-3024 The Department of Marriage and Family Therapy offers an M.A. and a Ph.D. and provides training in marriage and family therapy theory, research

Raina, Ramesh

424

Child And Family Studies Department Of Child And Family Studies  

E-print Network

sexuality) and family development (i.e., parenting, marriage, domestic violence). CFS also offers minorsChild And Family Studies Department Of Child And Family Studies Robert P. Moreno, Chair, 315 UNDERGRADUATE Robert P. Moreno, Undergraduate Program Director, 315-443-1715 The Department of Child and Family

Raina, Ramesh

425

Fostering Families' and Children's Rights to Family Connections  

ERIC Educational Resources Information Center

Recent federal legislation strengthens children's and families' rights to family-centered practice by increasing the responsibility of child welfare agencies to identify and engage extended family members in providing care and support to children placed out of the home. Preliminary results from an experimental study of a federally funded family

Landsman, Miriam J.; Boel-Studt, Shamra

2011-01-01

426

We Are Family: Using Diverse Family Structure Literature with Children  

ERIC Educational Resources Information Center

The structure of the American family has changed over the years. Although the traditional father, mother, child structure still dominates, other family patterns are emerging. In this article the authors present: (1) current statistics relating to diverse family structures; (2) reasons for using diverse family structure literature with children;…

Gilmore, Deanna Peterschick; Bell, Kari

2006-01-01

427

Child And Family Studies Department Of Child And Family Studies  

E-print Network

Child And Family Studies Department Of Child And Family Studies Ambika Krishnakumar, Chair, 315 Irene Kehres, Director of Undergraduate Studies, 315-443-9634 The Department of Child and Family Studies healthy family and child development. Students are involved in learning both in class and field

McConnell, Terry

428

Family Treatment Approaches to Alcoholism: Assessing the "Alcoholic Family."  

ERIC Educational Resources Information Center

Research and clinical support for the connections between alcohol abuse and the family milieu have generated increased interest in family treatment approaches to alcoholism. In assessing the "alcoholic family," the clinician must consider numerous aspects of family interaction which have been linked to abuse and to treatment outcomes. Results from…

Gomberg, Christopher A.; Billings, Andrew G.

429

All in the Family? Family Environment Factors in Sibling Violence  

Microsoft Academic Search

Sibling violence is presumed to be the most common form of family violence and the least studied. Based on data from “Physical\\u000a Violence in American Families, 1976,” this paper assesses the family environment factors associated with sibling physical\\u000a violence. Of a range of potential family influences, measures of family disorganization were the most significant predictors\\u000a of sibling violence, overriding the

Shelley Eriksen; Vickie Jensen

2006-01-01

430

Family processes and adolescent adjustment in intact and remarried families  

Microsoft Academic Search

This study examines whether family processes that predict positive and negative developmental outcomes are the same in intact and remarried families. Surveys were administered to 758 tenth graders from intact families and 95 from stepfather families. Measures of cohesion, democratic decision-making style, permissiveness, and conflict were used to predict self-rated depression, worry, and self-esteem. Remarried and intact families provide similar

Bonnie L. Barber; Janice M. Lyons

1994-01-01

431

Familial Hepatitis and Chronic Jaundice  

PubMed Central

The author reports the history of a family of six children, of whom two, the eldest and the fifth, are normal; three died, a boy when 6 months old and two girls when 9 and 10 years old, from the same familial disease that also attacked another boy now 7 years old. The essential features of this disease are hypertrophy of both liver and spleen, chronic icterus with evidence of salts and bile-pigments in the blood and urine, retardation of physical, mental, and sexual development, slight deafness in one case and clubbing of the fingers in another. This condition is a good example of biliary cirrhosis of the liver. After reviewing recent French observations, the author recalls the large contribution of English authors on the subject. He then distinguishes three types of familial cirrhosis: Laennec's type with enlarged liver, the type of splenomegalic anascitic and anicteric cirrhosis, resembling Banti's syndrome, and the commonest type or biliary cirrhosis. The author describes particular histological lesions, and when dealing with differential diagnoses, excludes dyslipoidic, polycoric, and other acquired cirrhosis in children. He then summarizes the relationships between this disease and the obstructive cirrhosis to a congenital defect of the bile-ducts, the cirrhosis in young Indians, the syndrome of hepatic lenticular degeneration, and the syndrome of cirrhosis of the liver combined with hæmangiomatosis. Finally, after recalling the close analogy of the condition with renal dwarfism, the author shows how the interpretation of these relationships may throw light on the pathogenesis of various progressive congenital diseases. PMID:19992037

Debré, Robert

1939-01-01

432

Measuring Family Reunion Travel Motivations  

Microsoft Academic Search

The study developed a Family Reunion Travel Motivation Scale (FRTMS) measuring family reunion travelers’ motivations. Through a rigorous scale development process, the final model of the scale exhibits excellent levels of psychometric properties. Details of each step are described in this paper. The 15-items scale contains four dimensions labeled as: (a) family history and togetherness, (b) immediate family cohesion, (c)

Juyeon Y. Kluin; Xinran Y. Lehto

433

Marriage and Family Therapy Assessment.  

ERIC Educational Resources Information Center

Reviews a number of inventories designed to measure dimensions of family systems theory and then provides a discussion of family systems assessment. Includes discussions of two couple's inventories, eight nuclear family inventories, and two family of origin inventories. Concludes that counselor educators must have understanding of marriage and…

West, John D.

1988-01-01

434

Changes in American Family Life  

ERIC Educational Resources Information Center

This article attempts to provide a factual, historical perspective on the current family situation of American children. Demographic statistics from recent decades are given which show trends toward small family size, nuclear families, one-parent families, and a higher level of education among parents. (MS)

Norton, Arthur J.; Glick, Paul C.

1976-01-01

435

The Power of Family Literacy.  

ERIC Educational Resources Information Center

This report presents the early findings from the analysis of a family literacy demonstration project under the direction of the National Center for Family Literacy. The data in this report are based upon the experiences of over 300 families who participated in the Toyota Families for Learning Program during the 1992-1993 school year. The first…

National Center for Family Literacy, Louisville, KY.

436

Stable Black Families. Final Report.  

ERIC Educational Resources Information Center

This document is the final report of a study conducted to determine what factors contribute to strong Black family life and how these strong families solve problems, in order to add to the knowledge base on stable families so as to enhance practical intervention with families in need, and to identify models of self-help strategies used by stable…

Gary, Lawrence E.; And Others

437

Trends in Family Child Care  

ERIC Educational Resources Information Center

The author presents insights from various readers of "ExchangeEveryDay" regarding trends in the world of family child care. Kathleen Reticker of Acre Family Child Care in Lowell, Massachusetts thinks an increasing trend in Family Child Care is the pressure to emulate a Center, instead of seeing family child care as a different model. Over the…

Neugebauer, Roger

2011-01-01

438

IRAS asteroid families  

NASA Technical Reports Server (NTRS)

The Infrared Astronomical Satellite (IRAS) sampled the entire asteroid population at wavelengths from 12 to 100 microns during its 1983 all sky survey. The IRAS Minor Planet Survey (IMPS) includes updated results for more recently numbered as well as other additional asteroids with reliable orbital elements. Albedos and diameters were derived from the observed thermal emission and assumed absolute visual magnitudes and then entered into the IMPS database at the Infrared Processing and Analysis Center (IPAC) for members of the Themis, Eos, Koronis and Maria asteroid families and compared with their visual colors. The IMPS results for the small (down to about 20 km) asteroids within these major families confirm trends previously noted for their larger members. Each of these dynamical families which are defined by their similar proper elements appears to have homogeneous physical properties.

Veeder, G. J.; Williams, J. G.; Tedesco, E. F.; Matson, D. L.

1991-01-01

439

Preservation and Modification of Culture in Family Socialization: Development of Parenting Measures for Korean Immigrant Families  

PubMed Central

This study aims to describe the family socialization beliefs and practices of Korean immigrant parents through testing psychometric properties of several newly developed items and scales to assess the major components of the Korean traditional concept of family socialization, ga-jung-kyo-yuk. These new measures were examined for validity and reliability. The findings show that Korean immigrant parents largely preserve their traditional and core parenting values, while also showing meaningful, yet not very dramatic, signs of adopting new cultural traits. The results also suggest that the acculturative process may not be simply bilinear but may generate a new, unique and blended value and behavior set from the two (or more) cultures involved. Culturally appropriate practice requires not only further validation of existing knowledge with minority groups, but the development of a theoretical framework of family socialization that recognizes the cultural uniqueness of immigrant families. PMID:24765236

Choi, Yoonsun; Kim, You Seung; Drankus, Dina; Kim, Hyun Jee

2012-01-01

440

Family Complexity among Children in the United States  

PubMed Central

Researchers largely have relied on a measure of family structure to describe children’s living arrangements, but this approach captures only the child’s relationship to the parent(s), ignoring the presence and composition of siblings. We develop a measure of family complexity that merges family structure and sibling composition to distinguish between simple two-biological-parent families, families with complex-sibling (half or stepsiblings) arrangements, and complex-parent (stepparent, single-parent) families. Using the Survey of Income and Program Participation (SIPP), we provide a descriptive profile of changes in children’s living arrangements over a 13-year span (1996–2009). SIPP sample sizes are sufficiently large to permit an evaluation of changes in the distribution of children in various (married, cohabiting, and single-parent) simple and complex families according to race/ethnicity and parental education. The article concludes by showing that we have reached a plateau in family complexity and that complexity is concentrated among the most disadvantaged families. PMID:25332509

MANNING, WENDY D.; BROWN, SUSAN L.; STYKES, J. BART

2014-01-01

441

1.OA Fact Families  

NSDL National Science Digital Library

This is a task from the Illustrative Mathematics website that is one part of a complete illustration of the standard to which it is aligned. Each task has at least one solution and some commentary that addresses important asects of the task and its potential use. Here are the first few lines of the commentary for this task: Materials * Fact Family work sheets * Blank addition and subtraction frames (2 of each) * Numbers cards in fact-family sets Actions As a whole class, t...

442

Family violence: guidelines for recognition and management  

PubMed Central

Chronic and intermittent abuse of one family member by another is common. Victims may be children who are sexually or physically abused, wives or live-in partners, or older relatives. Physicians are often the first points of contact for patients who have been abused, but the abuse is frequently concealed by the victims. Physicians should be alert to signs of battering such as bruises in various stages of healing, unusual behaviour in children and interpersonal difficulties in the family. There are a number of options in prevention and treatment, including referral to social service and legal authorities, calling on other resources in the family and helping the individual develop coping skills. This review also lists a large number of social agencies in Canada that are willing to help victims of abuse. PMID:3971273

Ghent, William R.; Da Sylva, Normand P.; Farren, Margo E.

1985-01-01