Predicting CO2 production of lactating dairy cows from animal, dietary, and production traits using an international dataset.

Automated measurements of the ratio of concentrations of methane and carbon dioxide, [CH4]:[CO2], in breath from individual animals (the so-called "Sniffer-technique") and estimated CO2 production can be used to estimate CH4 production, provided that CO2 production can be reliably calculated. This would allow CH4 production from individual cows to be estimated in large cohorts of cows, whereby ranking of cows according to their CH4 production might become possible and their values could be used for breeding of low CH4 emitting animals. Estimates of CO2 production are typically based on predictions of heat production, which can be calculated from body weight (BW), energy-corrected milk yield, and days of pregnancy. The objectives of the present study were to develop predictions of CO2 production directly from milk production, dietary, and animal variables, and furthermore develop different models to be used for different scenarios, depending on available data. An international data set with 2,244 records from individual lactating cows including CO2 production and associated traits, as dry matter intake (DMI), diet composition, BW, milk production and composition, days in milk and days pregnant, was compiled to constitute the training data set. Research location and experiment nested within research location were included as random intercepts. The method of CO2 production measurement (respiration chamber (RC) or GreenFeed (GF)) was confounded with research location, and therefore excluded from the model. In total, 3 models were developed based on the current training data set: Model 1 ("Best Model"), where all significant traits were included, Model 2 ("On-Farm Model"), where DMI was excluded, and Model 3 ("Reduced On-Farm Model"), where both DMI and BW were excluded. Evaluation on test data sets either with RC data (n = 103), GF data without additives (n = 478) or GF data only including observations where nitrate, 3-nitrooxypropanol (3-NOP), or a combination of nitrate and 3-NOP were fed to the cows (GF+: n = 295), showed good precision of the 3 models, illustrated by low slope bias both in absolute values (-0.22 to 0.097) and in percentage (0.049 to 4.89) of mean square error (MSE). However, the mean bias (MB) indicated systematic over-prediction and under-prediction of CO2 production when the models were evaluated on the GF and the RC test data set, respectively. To address this bias, the 3 models were evaluated on a modified test data set, where the CO2 production (g/d) was adjusted by subtracting (where measurements were obtained by RC) or adding absolute MB (where measurements were obtained by GF) from evaluation of the specific model on RC, GF, and GF+ test data sets. By this modification, the absolute values of MB and MB as percentage of MSE became negligible. In conclusion, the 3 models were precise in predicting CO2 production from lactating dairy cows.

Development and comparison of a generic multiple-locus variable-number tandem repeat analysis with pulsed-field gel electrophoresis for typing of Salmonella enterica subsp. enterica.

AIMS: Salmonella enterica subsp. enterica causes salmonellosis in humans and animals. Serovar-specific multiple-locus variable-number tandem repeat analysis (MLVA) is widely used for Salmonella surveillance; however, isolates have to be serotyped prior to MLVA typing and only the most common serovars can be typed. We developed a MLVA scheme for high-discriminatory typing of Salmonella. METHODS AND RESULTS: Sixty-six unique VNTRs were investigated and the polymorphisms of seven promising VNTRs were evaluated with a panel 163 diverse isolates of 14 serotypes of significance for human health. Five VNTRs were selected for MLVA analysis. The discriminatory power was evaluated within serovars by 163 isolates and MLVA yielded 79 genotypes (DI of 0·9790) and pulsed-field gel electrophoresis (PFGE) revealed 87 genotypes (DI of 0·9989). MLVA divided each serotype into 2-8 different profiles and identified six pairs of outbreak-related strains. CONCLUSIONS: The technique showed a high-discriminatory power within most serotypes comparable with or better than that of PFGE. SIGNIFICANCE AND IMPACT OF THE STUDY: This MLVA assay makes it possible to use a single typing method for Salmonella surveillance and outbreak investigations. This allows inexpensive and fast surveillance for laboratories without resources for both serotyping and molecular typing, e.g. PFGE or sequence-based methods, and thereby improve the effectiveness of epidemiological investigations of Salmonella infections globally.

Multiple-locus variable-number tandem repeat analysis of Salmonella enterica subsp. enterica serovar Dublin.

AIMS: Salmonella serovar Dublin causes disease in cattle and leads to considerable production losses. In humans, severe invasive disease and high mortality rates are reported. The presently available typing methods provide insufficient discrimination within Salm. Dublin for epidemiological investigations. In this study, we developed a multiple-locus variable-number tandem repeat analysis (MLVA) scheme for high discriminatory typing of Salm. Dublin. METHODS AND RESULTS: Nine loci of variable number of tandem repeats (VNTRs) were evaluated based on a panel of 40 diverse isolates. The four most discriminative VNTRs were selected for further MLVA analysis. The discriminatory power was evaluated on 272 veterinary and human isolates plus 29 outbreak-related isolates. MLVA divided the 272 isolates into 103 types and successfully identified isolates from an epidemiologically confirmed outbreak. VNTRs exhibited 100% in vitro stability and contained only true repeats. The discriminatory power of the MLVA was compared to pulsed-field gel electrophoresis (PFGE). When analysing a subset of 106 isolates, MLVA obtained 60 types (index of diversity (DI) of 0·97), while PFGE revealed 10 types (DI of 0·57). CONCLUSIONS: The technique showed a significantly enhanced discriminatory power compared with the current 'gold standard' PFGE. MLVA is a fast and low-cost method. SIGNIFICANCE AND IMPACT OF THE STUDY: This MLVA method can be recommended to be used in routine subtyping of isolates for outbreak investigations and disease surveillance. The method may provide valuable additional information that can improve the effectiveness of epidemiological investigations of Salm. Dublin infections in patients as well as in the primary production and thereby contribute to the efforts of reducing transmission of infection.

A long-lasting outbreak of Salmonella Typhimurium U323 associated with several pork products, Denmark, 2010.

This paper shows that control of foodborne disease outbreaks may be challenging even after establishing the source of infection. An outbreak of Salmonella Typhimurium U323 infections occurred in Denmark from March to September 2010, involving 172 cases. Before the detection of human cases, several positive isolates of the outbreak strain had been found in a particular pig slaughterhouse and thus early traceback, investigation and control measures were possible. Several batches of pork and pork products were recalled and the slaughterhouse was closed twice for disinfection. No single common food item was identified as the outbreak source, but repeated isolation of the outbreak strain from the slaughterhouse environment and in pork and products as well as patient interviews strongly suggested different pork products as the source of infection. Furthermore, a matched case-control study identified a specific ready-to-eat spreadable pork sausage (teewurst) as the source of a sub-outbreak (matched odds ratio 17, 95% confidence interval 2·1-130).

The occurrence and characteristics of auras in a large epilepsy cohort.

OBJECTIVES: Despite several studies, estimates of the frequency with which auras occur in conjunction with epilepsy continue to be imprecise. The aim of this study was to assess the occurrence and characteristics of auras in a large population-based epilepsy cohort. MATERIALS AND METHODS: Subjects with verified epilepsy were recruited from population-based twin registries in the USA, Denmark and Norway. Using a structured interview in which a list of auras was provided, subjects were asked about the warning symptoms preceding their epileptic attacks. RESULTS: 31% of the total sample (n = 1897) and 39% of those with active epilepsy (n = 765) had experienced an aura. Six percent reported more than one type. Non-specified auras were most frequently reported (35%), followed by somatosensory (11%) and vertiginous (11%). While the majority of those reporting auras (59%) had focal epilepsies, auras of a mostly non-specific nature were experienced by 13% of those with generalized epilepsies. CONCLUSION: Auras serve an important purpose in that they may prevent seizure-related injuries and could provide an indication as to where the seizures originate. The occurrence of auras often is underestimated, especially in children and those with learning disabilities.

Genetic screening of Scandinavian families with febrile seizures and epilepsy or GEFS+.

BACKGROUND: Mutations in the three genes SCN1A, SCN1B and GABRG2, all encoding subunits of ion channels, have been known to cause generalized epilepsy with febrile seizures plus (GEFS+) in families of different origin. OBJECTIVE: To study the occurrence of mutations in these genes in families with GEFS+ or a GEFS+ resembling phenotype of Scandinavian origin. MATERIAL AND METHODS: We performed linkage analysis in 19 Scandinavian families with a history of febrile seizures (FS) and epilepsy or GEFS+. Where linkage could not be excluded, the genes of interest were sequenced. RESULTS: We identified only one mutation in SCN1A, which seems to be a rare variant with no functional consequence. CONCLUSION: This suggests that mutations in these three genes are not a prevalent cause of familial cases of FS and epilepsy or GEFS+ in Scandinavia.

Detection of mutations in the COL4A5 gene by SSCP in X-linked Alport syndrome.

Alport syndrome is a progressive renal disease leading to chronic renal failure, which often is accompanied by sensorineural deafness and ophthalmological signs in the form of anterior lenticonus. The X-linked form of the disease is caused by mutations in the COL4A5 gene encoding the alpha5-chain of type IV-collagen. We performed mutation analysis of the COL4A5 gene by PCR-SSCP analysis of each of the 51 exons with flanking intronic sequences in 81 patients suspected of X-linked Alport syndrome including 29 clear X-linked cases, 37 cases from families with a pedigree compatible with X-linked inheritance, and 15 isolated cases. We found a mutation detection rate of 52% (42/81) (58% in males and 21% in females), and 69% (20/29) in families who clearly demonstrated X-linked inheritance. Thirty-six different mutations were found in 42 patients comprising 16 missense mutations, seven frameshifts, three in-frame deletions, four nonsense mutations, and six splice site mutations. Twenty-two of the mutations have not previously been reported. Furthermore, we found one non-pathogenic amino acid substitution, one rare variant in a non-coding region, and one polymorphism with a heterozygosity of 28%. Three de novo mutations were found, two of which were paternal and one of maternal origin.

Genetic and environmental factors in epilepsy: a population-based study of 11900 Danish twin pairs.

The contribution of genetic and environmental factors to the occurrence of epilepsy was examined in an unselected sample of twins recruited from the population-based Danish Twin Registry. Information on the occurrence of epilepsy in both members of a twin pair was obtained from 11900 pairs whose ages ranged from 12 to 41 years. Concordance rates, odds ratios and tetrachoric correlations were used to quantify the similarity of monozygotic (MZ) and dizygotic (DZ) twins. The sample was stratified by sex and separated into two age cohorts for analysis. Significantly higher probandwise concordance rates were found for MZ compared with DZ twins (0.37 and 0.08, P<0.01). Odds ratios and tetrachoric correlation showed similar pattern. An etiological model including additive genetic and individual specific environmental factors provided the best overall fit to the data, with 70 and 88% of the liability to develop epilepsy being accounted for by genetic factors in the younger and older cohorts, respectively. Individual specific environmental factors explained the remaining 30 and 12%, respectively. In conclusion, this study has confirmed the substantial impact, which genetic factors have in the etiology of epilepsy. The heritability of epilepsy is high and seems to increase with age.

Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency.

ABSTRACT Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is considered a rare inherited mitochondrial fatty acid oxidation disorder. Less than 10 patients have been reported, diagnosed on the basis of ethylmalonic aciduria and low SCAD activity in cultured fibroblast. However, mild ethylmalonic aciduria, a biochemical marker of functional SCAD deficiency in vivo, is a common finding in patients suspected of having metabolic disorders. Based on previous observations, we have proposed that ethylmalonic aciduria in a small proportion of cases is caused by pathogenic SCAD gene mutations, and SCAD deficiency can be demonstrated in fibroblasts. Another - much more frequent - group of patients with mild ethylmalonic aciduria has functional SCAD deficiency due to the presence of susceptibility SCAD gene variations, i.e. 625G>A and 511C>T, in whom a variable or moderately reduced SCAD activity in fibroblasts may still be clinically relevant. To substantiate this notion we performed sequence analysis of the SCAD gene in 10 patients with ethylmalonic aciduria and diagnosed with SCAD deficiency in fibroblasts. Surprisingly, only one of the 10 patients carried pathogenic mutations in both alleles, while five were double heterozygotes for a pathogenic mutation in one allele and the 625G>A susceptibility variation in the other. The remaining four patients carried only either the 511C>T or the 625G>A variations in each allele. Our findings document that patients carrying these SCAD gene variations may develop clinically relevant SCAD deficiency, and that patients with even mild ethylmalonic aciduria should be tested for these variations.

Evaluation of patients with symptoms suggestive of chronic polyneuropathy.

OBJECTIVES: The aim of this study was to determine the diagnostic yield and to describe the spectrum of diagnosis encountered by evaluation of patients with symptoms suggestive of chronic polyneuropathy. METHODS: We prospectively evaluated 198 patients referred to a department of neurology with symptoms suggestive of polyneuropathy. The evaluation included nerve conduction studies with near-nerve technique, quantitative examination of temperature sensation, blood tests, chest x-rays, and skin biopsies as well as diagnostic tests for differential diagnoses. RESULTS: Polyneuropathy was found in 147 patients, alternative diagnoses in 25, and 26 remained undiagnosed. The etiology of polyneuropathy could not be identified in 25% of the patients with polyneuropathy. In the remaining 75%, the cause of neuropathy was diabetes and/or alcohol abuse (41%), monoclonal gammopathy of undetermined significance (5%), drugs (5%), connective tissue disease (3%), and a number of less frequent conditions. A previously undiagnosed condition was found in 30% of the patients with polyneuropathy. CONCLUSION: Evaluation of patients with symptoms suggestive of polyneuropathy reveals a high fraction of patients with previously undiagnosed conditions both in patients ending up with a polyneuropathy diagnosis and those without this diagnosis.

Diagnostic yield by testing small fiber function in patients examined for polyneuropathy.

We assessed the diagnostic yield of adding quantitative sensory testing to the standard work-up for polyneuropathy in unselected patients. All patients aged 18 to 70 years referred to our department for electrodiagnosis with a tentative diagnosis of polyneuropathy and symptoms complying with predefined criteria were included in the study. We performed near nerve conduction studies in 4 nerves and determined heat and cold detection thresholds on hand and foot with a Thermotest (Somedic AB, Sweden). In order to uncover CNS diseases, somatosensory-evoked potentials were recorded in patients with abnormal quantitative sensory testing and normal nerve conduction studies. A total of 198 patients completed the study and 149 were considered to have polyneuropathy. Twenty-five patients remained undiagnosed and in 24 patients, other diseases were responsible for the symptoms. Of the patients with either polyneuropathy or no other diagnosis, 76% (n = 174) had abnormal nerve conduction. Abnormal cold sensation, heat sensation or abnormality in at least 1 of these and normal nerve conduction were found in 14, 12 and 17 patients. Of the 174 patients, 86% (95% CI 80-90%) had an abnormality in at least 1 of the tests (i.e. abnormal nerve conduction and/or abnormal quantitative testing of temperature sensation). In conclusion, quantitative testing of temperature sensation improves the diagnostic yield in patients examined for chronic polyneuropathy.

Inducible nitric oxide synthase expression in periodontitis.

Recently, nitric oxide (NO) has been shown to be vital in inflammatory processes. Nitric oxide synthase (NOS) exists in three different isoforms, two constitutively produced with physiological roles, and an inducible form, iNOS, which is involved in inflammation. This study examined the localisation of iNOS in biopsies from patients with periodontitis using immunohistochemistry, and compared these with healthy tissue biopsies. Biopsies were obtained from 16 periodontitis patients undergoing periodontal surgery and from clinically healthy tissues of 5 patients having crown lengthening procedures. The periodontitis diseased tissue demonstrated a greater level of iNOS expression than the healthy tissue. The source of iNOS in the periodontal tissues was determined by our monoclonal antibody to be the macrophage, with the endothelial cells also contributing. A role for NO in the inflammatory response of periodontal tissues is suggested, but the precise role requires further elucidation.

Cerebral infarct following carotid endarterectomy. Frequency, clinical and hemodynamic significance evaluated by MRI and TCD.

The purpose of this study was to disclose the frequency of new infarcts after Carotid Endarterectomy (CEA) by MRI and Transcranial Doppler examinations (TCD), and to evaluate the clinical and pathological significance. Of a consecutive series of 41 patients with a symptomatic carotid stenosis exceeding 69%, 33 had MRI and TCD examinations performed before and after the CEA. Pre-operative MRIs revealed Focal High Signal Intensity (FHSI) in 21 patients (64%) on the side of the stenosis, ranging in number from 2 to more than 20 and in size from 0.5 cm to more than 3 cm. After the operation 8 patients (24%) each had acquired from 1-4 new FHSIs, but only 3 patients (9%) suffered from clinical symptoms. In 2 patients, who had had a stroke, the FHSIs were more than 3 cm. In 1 patient, who experienced a Transient Ischemic Attack (TIA), the FHSI was 1-2 cm. The TCD disclosed low Pulsatility Index (PI) values in 2 of the 3 patients who had new FHSIs and clinical symptoms. In all the patients who did not show new FHSIs after the operation, the PI was normal in the MCA of the symptomatic hemisphere after CEA. So new cerebral FHSIs were rather frequent after a CEA, but only FHSIs >1 cm were accompanied by a TIA or stroke, and a low PI in the MCA of the relevant hemisphere was found before or in connection with the operation in 2 of the 3 patients who developed clinical symptoms.

A novel missense mutation (402C-->T) in exon 1 in the EDA gene in a family with X-linked hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia (EDA), or Christ-Siemens-Touraine syndrome, is clinically characterized by hypohidrosis, hypoodontia and hypotrichosis. The X-linked form of the disease has been mapped to Xq12-q13.1, and a gene from this region has recently been cloned. This gene encodes a predicted transmembrane protein of 135 amino acids, which was found to be expressed in keratinocytes, hair follicles, and sweat glands. A variety of rearrangements in this gene have been found in patients with hypohidrotic ectodermal dysplasia. We have screened the probands from nine unrelated Danish families with hypohidrotic ectodermal dysplasia for mutation in exon 1 of the EDA-gene by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). In one large kindred we identified a novel missense mutation (402C-->T), which changes a histidine to tyrosine at position 54 in the protein. This mutation cosegregates with the disease in the family and is the first mutation described which affects the predicted transmembrane, hydrophobic domain of the protein.

Structural organization of the human short-chain acyl-CoA dehydrogenase gene.

Short-chain acyl-CoA dehydrogenase (SCAD) is a homotetrameric mitochondrial flavoenzyme that catalyzes the initial reaction in short-chain fatty acid beta-oxidation. Defects in the SCAD enzyme are associated with failure to thrive, often with neuromuscular dysfunction and elevated urinary excretion of ethylmalonic acid (EMA). To define the genetic basis of SCAD deficiency and ethylmalonic aciduria in patients, we have determined the sequence of the complete coding portion of the human SCAD gene (ACADS) and all of the intron-exon boundaries. The SCAD gene is approximately 13 kb in length and consists of 10 exons. Four polymorphic sites have previously been detected by sequencing of cDNA from fibroblasts of patients excreting elevated amounts of EMA. Three of these polymorphisms (321T/C, 990C/T, 1260G/C) are silent variants, while a 625G/A polymorphism results in an amino acid replacement and has been shown to be associated with ethylmalonic aciduria. From analysis of 18 unrelated Danish families, we show that the four SCAD gene polymorphisms constitute five allelic variants of the SCAD gene, and that the 625A variant together with the less frequent variant form of the three other polymorphisms (321C, 990T, 1260C) constitutes an allelic variant with a frequency of 22% in the general Danish population. Using fluorescence in-situ hybridization, we confirm the localization of the human SCAD gene to the distal part of Chromosome (Chr) 12 and suggest that the SCAD gene is a single-copy gene. The evolutionary relationship between SCAD and five other members of the acyl-CoA dehydrogenase family was investigated by two independent approaches that gave similar phylogenetic trees.

Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.

Inhibition of Prevotella and Capnocytophaga immunoglobulin A1 proteases by human serum.

Oral Prevotella and Capnocytophaga species, regularly isolated from periodontal pockets and associated with extraoral infections, secret specific immunoglobulin A1 (IgA1) proteases cleaving human IgA1 in the hinge region into intact Fab and Fc fragments. To investigate whether these enzymes are subject to inhibition in vivo in humans, we tested 34 sera from periodontally diseased and healthy individuals in an enzyme-linked immunosorbent assay for the presence and titers of inhibition of seven Prevotella and Capnocytophaga proteases. All or nearly all of the sera inhibited the IgA1 protease activity of Prevotella buccae, Prevotella oris, and Prevotella loescheii. A minor proportion of the sera inhibited Prevotella buccalis, Prevotella denticola, and Prevotella melaninogenica IgA1 proteases, while no sera inhibited Capnocytophaga ochracea IgA1 protease. All inhibition titers were low, ranging from 5 to 55, with titer being defined as the reciprocal of the dilution of serum causing 50% inhibition of one defined unit of protease activity. No correlation between periodontal disease status and the presence, absence, or titer of inhibition was observed. The nature of the low titers of inhibition in all sera of the IgA1 proteases of P. buccae, P. oris, and P. loescheii was further examined. In size exclusion chromatography, inhibitory activity corresponded to the peak volume of IgA. Additional inhibition of the P. oris IgA1 protease was found in fractions containing both IgA and IgG. Purification of the IgG fractions of five sera by passage of the sera on a protein G column resulted in recovery of inhibitory IgG antibodies against all three IgA1 proteases, with the highest titer being for the P. oris enzyme. These finding indicate that inhibitory activity is associated with enzyme-neutralizing antibodies.

Biased expression of T cell receptor V beta genes in periodontitis patients.

The aim of the present study was to investigate the hypothesis that there is selective activation and expansion of a limited repertoire of T cell receptor (TCR)-bearing T cells in periodontitis tissue. We studied TCR V beta gene expression in gingival tissues of periodontitis lesions and compared these with peripheral blood mononuclear cells (PBMC) from the same patients using polymerase chain reaction (PCR) amplification with 22 V beta-specific sense primers in combination with a common antisense C beta-specific primer. After initial therapy, gingival tissue specimens were obtained from 14 periodontitis patients at the time of periodontal surgery, and PBMC were also obtained from the same patients by density gradient centrifugation. Total RNA was extracted and analysed by reverse transcription PCR. The PCR products were electrophoresed on a 2% agarose gel and stained with ethidium bromide. For each product, gingival tissue and the respective peripheral blood were compared. The TCR repertoire identified in the PBMC in general overlapped with that of the gingival tissue. However, V beta 6 appeared to be over-expressed in the gingival tissues compared with the PBMC, but V beta 16 appeared to be under-expressed in the gingival tissues. Although it is not known whether this is due to antigen-specific activation or superantigen activation, the data suggest that there may be as yet uncharacterized T cell subsets in periodontal disease tissue.

[Genetic aspects of epilepsy]. / Genetiske aspekter ved epilepsi.

Accumulating evidence suggests a significant proportion of the forms of epilepsy to be genetically determined. Several epilepsy syndromes have been mapped on the human genome, though their molecular basis remains unknown. Technical advances in molecular biology now provide a basis for improving our understanding of the molecular mechanisms involved in genetically determined types of epilepsy Genetic mapping will improve the accuracy of genetic counselling. Improved insight into the molecular biology may help to elucidate the underlying epileptogenic mechanisms and pave the way for new developments in pharmacological control of epileptic seizures. Further advances in research on genetics and epilepsy will require national and international cooperation between epileptologists and geneticists in search of informative families for linkage analysis.