The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia.

Formation of the secondary palate is a complex step during craniofacial development. Disturbance of the events affecting palatogenesis results in a failure of the palate to close. As a consequence of deformity, an affected child will have problems with feeding, speech, hearing, dentition and psychological development. Cleft palate occurs frequently, affecting approximately 1 in 1,500 births; it is usually considered a sporadic occurrence resulting from an interaction between genetic and environmental factors. Although several susceptibility loci have been implicated, attempts to link genetic variation to functional effects have met with little success. Cleft palate with ankyloglossia (CPX; MIM 303400) is inherited as a semidominant X-linked disorder previously described in several large families of different ethnic origins and has been the subject of several studies that localized the causative gene to Xq21 (refs. 10-13). Here we show that CPX is caused by mutations in the gene encoding the recently described T-box transcription factor TBX22 (ref. 14). Members of the T-box gene family are known to play essential roles in early vertebrate development, especially in mesoderm specification. We demonstrate that TBX22 is a major gene determinant crucial to human palatogenesis. The spectrum of nonsense, splice-site, frameshift and missense mutations we have identified in this study indicates that the cleft phenotype results from a complete loss of TBX22 function.

Correction to one of MacArthur's species-abundance formulas.

The expected relative abundances of the commoner species in a biological population are less if the niches are overlapping than if they are non-overlapping. MacArthur's mathematical arguments, which lead to the opposite conclusion, are incorrect.

Characteristics of functional movement screening testing in elite handball players: Indicative data from the 9.

OBJECTIVES: To test 9 + screening batterie's intra-rater reliability, to provide indicative data of elite handball players, and to analyze difference between age, playing positions and level of play. DESIGN: Descriptive study. SETTING: Icelandic elite male handball players. PARTICIPANTS: 182 elite male handball players. MAIN OUTCOME MEASURES: Nine + screening battery. RESULTS: Reliability test: Intra-class correlation for the total score was 0.95. The correlation of each of the test factors varied from 0.63 to 0.91. The mean total score was 22.3 ±â€¯2.9 (95%CI 16.7-28.1), with no difference in total score comparing players age or level of play. Goalkeepers displayed a higher total score than other players (F3,151 = 5.75, p = 0.001). Junior players had a lower score than senior players in tests measuring abdominal strength and core stability; Test 5; │2(3, 182) = 41.5, p < 0.0001, Test 6; │2(3, 182) = 55.7, p < 0.0001, Test 7; │2(3, 182) = 11.8, p < 0.005, but higher scores in tests measuring trunk and shoulder mobility Test 8; │2(3, 182) = 18.2, p < 0.0001, Test 9; │2(3, 182) = 22.2, p = 0.006. CONCLUSIONS: The 9+ intra-rater reliability was acceptable for the total score and individual tests. Age-related differences were provided in many individual tests.

Sex hormone concentrations in blood serum from the north Atlantic fin whale (Balaenoptera physalus).

Blood serum concentrations of testosterone and progesterone were measured in postmortem samples taken at sea from 814 fin whales (Balaenoptera physalus) caught during the summers (June-September) of 1981-1989. The ages of 781 of these animals were also assessed. The testosterone concentrations in samples from 352 males averaged 2 nmol/l; 41 samples had concentrations of 0.1 nmol/l or lower and 34 of these came from whales aged between 2 and 14 years and showed a Gaussian type of age distribution with a peak number at 7 to 8 years. The mean testosterone concentrations in the males increased by more than fourfold between June and August. Serum progesterone concentrations of the 462 females fell into three separate groups: (1) group I with values < or = 0.1 nmol/l; (2) group II with intermediate values of > 0.1 nmol/l but < 10 nmol/l; (3) group III with values of > or = 10 nmol/l. These three groups of females seemed to consist respectively of young sexually immature females, mature non-pregnant females and pregnant females. The age distribution in the groups indicated that puberty in females is attained chiefly between the ages of 7 and 10. The yearly pregnancy rate (that percentage of all females caught and studied in a year which had progesterone values > or = 10 nmol/l) was between 35% and 55%, except in 1987 when it was 67%. The yearly pregnancy rate would range from 56% to 93% if only mature females (i.e. those with serum progesterone > 0.1 nmol/l) were considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of head injuries in elite football.

OBJECTIVES: The aim of this study was to describe, using video analysis, the mechanisms of head injuries and of incidents with a high risk of head injury in elite football. METHODS: Videotapes and injury information were collected prospectively for 313 of the 409 matches played in the Norwegian (2000 season) and Icelandic (1999 and 2000 season) professional leagues. Video recordings of incidents where a player appeared to be hit in the head and the match was consequently interrupted by the referee were analysed and cross referenced with reports of acute time loss injuries from the team medical staff. RESULTS: The video analysis revealed 192 incidents (18.8 per 1000 player hours). Of the 297 acute injuries reported, 17 (6%) were head injuries, which corresponds to an incidence of 1.7 per 1000 player hours (concussion incidence 0.5 per 1000 player hours). The most common playing action was a heading duel with 112 cases (58%). The body part that hit the injured player's head was the elbow/arm/hand in 79 cases (41%), the head in 62 cases (32%), and the foot in 25 cases (13%). In 67 of the elbow/arm/hand impacts, the upper arm of the player causing the incident was at or above shoulder level, and the arm use was considered to be active in 61 incidents (77%) and intentional in 16 incidents (20%). CONCLUSIONS: This study suggests that video analysis provides detailed information about the mechanisms for head injuries in football. The most frequent injury mechanism was elbow to head contact, followed by head to head contact in heading duels. In the majority of the elbow to head incidents, the elbow was used actively at or above shoulder level, and stricter rule enforcement or even changes in the laws of the game concerning elbow use should perhaps be considered, in order to reduce the risk of head injury.

Evidence of Brucella infection in marine mammals in the North Atlantic Ocean.

Between 1983 and 1996 a total of 1386 samples of serum were taken from four species of seal and three species of whale in the waters west of Iceland, the area of pack-ice north-west of Jan Mayen, the northern coast of Norway and the Kola Peninsula, the waters west of Svalbard, and the Barents Sea; they were tested for the presence of anti-Brucella antibodies with an indirect ELISA (protein G conjugate). The positive sera were re-tested with classical brucellosis serological tests, such as the serum agglutination test, the EDTA-modified serum agglutination test, the Rose Bengal test, and the complement fixation test, as well as an anti-complement ELISA. Anti-Brucella antibodies were detected in all the species investigated, except for the bearded seal (Erignathus barbatus), with the following prevalences: hooded seals (Cystophora cristata) 35 per cent; harp seals (Phoca groenlandica) 2 per cent; ringed seals (Phoca hispida) 10 per cent; minke whales (Balaenoptera acutorostrata) 8 per cent; fin whales (Balaenoptera physalus) 11 per cent; and sei whales (Balaenoptera borealis) 14 per cent. An isolate belonging to the genus Brucella was obtained from the liver and spleen of one of the seropositive minke whales. The findings suggest that antibodies against the surface lipopolysaccharide of Brucella species are widely distributed among marine mammals in the North Atlantic Ocean.

Prevention of hamstring strains in elite soccer: an intervention study.

The purpose was to test the effect of eccentric strength training and flexibility training on the incidence of hamstring strains in soccer. Hamstring strains and player exposure were registered prospectively during four consecutive soccer seasons (1999-2002) for 17-30 elite soccer teams from Iceland and Norway. The first two seasons were used as baseline, while intervention programs consisting of warm-up stretching, flexibility and/or eccentric strength training were introduced during the 2001 and 2002 seasons. During the intervention seasons, 48% of the teams selected to use the intervention programs. There was no difference in the incidence of hamstring strains between teams that used the flexibility training program and those who did not [relative risk (RR)=1.53, P=0.22], nor was there a difference compared with the baseline data (RR=0.89, P=0.75). The incidence of hamstring strains was lower in teams who used the eccentric training program compared with teams that did not use the program (RR=0.43, P=0.01), as well as compared with baseline data for the same intervention teams (RR=0.42, P=0.009). Eccentric strength training with Nordic hamstring lowers combined with warm-up stretching appears to reduce the risk of hamstring strains, while no effect was detected from flexibility training alone. These results should be verified in randomized clinical trials.

Defective prevention of immune precipitation in autoimmune diseases is independent of C4A*Q0.

Increased prevalence of C4 null alleles is a common feature of autoimmune diseases. We have shown previously that complement-dependent prevention of immune precipitation (PIP) is defective in patients with systemic lupus erythematosus (SLE), and correlated this defect with C4A*Q0 and low levels of the C4A isotype. To further clarify the role of C4A in the aetiology of SLE, we now extend our studies to other diseases which have been associated with C4A*Q0. The frequency of C4A*Q0 was increased in Icelandic patients with coeliac disease (0.50; P < 0.001), Grave's disease (0.30; P = 0.002) and insulin-dependent diabetes mellitus (0.23; P = 0.04) and in British patients with dermatitis herpetiformis (0.42; P = 0.002) and this was reflected in low levels of C4A. In spite of this, PIP was normal in these patients, and in marked contrast to our previous observations on connective tissue diseases, PIP measurements in these patient groups correlated more strongly with levels of C4B (r = 0.51, P = 0.0000004) than C4A. Patients with increased levels of anti-C1q antibodies had significantly lower PIP than patients without such antibodies (P < 0.01) and a negative association of PIP with anti-C1q antibodies was also reflected in an increased prevalence (P = 0.006) and levels (P = 0.006) of anti-C1q antibodies in patients with subnormal PIP, as well as a negative correlation between PIP and anti-C1q antibodies (r = - 0.25, P = 0.02). These results show that the PIP defect cannot be explained by low levels of C4A alone and suggest that measurements of anti-C1q antibodies may be useful in future studies on the molecular cause of the PIP defect in autoimmune connective tissue disease.

Limited MHC polymorphism in whales.

Little is known about disease and genetic variation in aquatic mammalian species such as whales. In this paper human HLA class I and class II probes were used to study major histocompatibility complex (MHC) genes from two species of whale: Fin (Balaenoptera physalus) and Sei (B. borealis). Stronger signals were obtained on whale than on equivalent concentrations of mouse DNA. Evidence was obtained for several DRB-related genes, a DNA genes, one DQA gene, and multiple class I genes in whales. Interestingly, the whale genes, from the small panel studied, were less polymorphic than those of humans or mice. The aquatic environment of this mammalian species may be a unique factor in shaping its immune response through the MHC.

X-linked cleft palate and ankyloglossia in an Icelandic family.

Information was available on 293 family members and spouses of seven generations in an Icelandic family with high frequency of cleft of secondary palate and ankyloglossia. The authors have personally investigated 182 individuals in generations IV-VII and have drawn blood from over 100 members for genetic marker studies. The senior author, Dr. Björnsson, has operated on two-thirds of the affected individuals. Twenty-six family members had cleft palate (CP) and, of these, 19 (17 male and two females) had ankyloglossia as well (CP + A). Twenty females and one male had only ankyloglossia (A). All mothers in one of two branches of the family who had sons with CP + A had ankyloglossia themselves. This was not the case in the other branch, in which the mothers of affected sons were themselves unaffected. Fathers affected with CP, CP + A, or high vaulted palate (HVP) never had affected sons. As reported earlier, the condition has been mapped to the q13-q21 region of the X chromosome using restriction fragment length polymorphism (RFLP) techniques (Moore et al, 1987). Our conclusion is that this midline defect is X-linked but varies in the severity of expression.

Analysis of the C4 genes in baleen whales using a human cDNA probe.

We have used a human C4 cDNA probe to investigate the complement component C4 gene in four members of the family Balaenopteridae: fin whale (Balaenoptera physalus), sei whale (B. borealis), minke whale (B. acutorostrata), and bryde's whale (B. edeni). Restriction mapping of genomic DNA from the first three species suggests the presence of only one locus in these species, and also shows that the C4 genes in the three species are very similar. We have used 14 restriction endonucleases to investigate the restriction fragment length polymorphism (RFLP) of fin whales, 13 enzymes for sei whales, and 8 enzymes for the minke whale. No polymorphism was seen in DNA from the five minke whale samples, but Rsa I and Taq I restriction enzymes gave polymorphism in fin and sei whales whereas Hind III and Msp I restriction enzymes showed polymorphism in sei whales only. Only one bryde's whale sample was available for investigation. The study of DNA available from mother-fetus pairs from the two polymorphic species demonstrated a simple, two-allele transmission of RFLP alleles.

GLO polymorphism in Iceland.

The phenotypes of red cell glyoxalase I (GLO) were determined in two Icelandic population samples using starch-gel electrophoresis and high-voltage agarose-gel electrophoresis. The gene frequencies of 178 individuals were 0.46 for GLO1 and 0.54 for GLO2. In a group of Icelandic insulin-dependent diabetics the gene frequencies were found to be very similar. The evaluation of 30 mother-child pairs is also shown.

Estimation of age-specific breeding probabilities from capture-recapture data.

We provide a new method for estimating the age-specific breeding probabilities from recaptures or resightings of animals marked as young. Our method is more direct than previous methods and allows the modeler to fit and compare models where the age-specific breeding proportions are equal over different cohorts or are a function of external covariates.

Serum esterases of Icelanders. I. A "silent" pseudocholinesterase gene in an Icelandic family.

During an investigation of cousin marriages in Iceland, five brothers and sisters were found to be homozygous for the "silent" allele of plasma cholinesterase. Clinical information on two family members is presented and discussed, and the possibility of the presence of a "nearly silent" plasma esterase allele, in one of the family units investigated, is suggested.

Genetic variation at enzyme loci in North Atlantic minke whales, Balaenoptera acutorostrata.

Electrophoretic variation within and between North Atlantic minke whale samples (Balaenoptera acutorostrata) from West Greenland, Iceland, and Norway was investigated. In the West Greenland samples, 28 enzyme systems were examined, representing 36 loci, of which 6 were found to be polymorphic. In Icelandic and Norwegian samples, 22 enzyme systems were examined, representing 29 loci, of which 6 and 5 were found to be polymorphic, respectively. The average heterozygosity was 0.058 (SE = 0.024) in samples from West Greenland, 0.074 (SE = 0.028) in samples from Iceland, and 0.054 (SE = 0.023) in samples from Norway. No significant deviations from the expected Hardy-Weinberg genotypic frequencies, within samples taken from the same area, were found. Significant differences in allele frequencies were observed, however, between samples from the three different areas. The average Nei's genetic distance was 0.014 and the average Fst value was 0.126. The genetic differences between the samples from the different areas indicate that those from West Greenland, Iceland, and Norway represented different breeding populations.

Soccer injuries in Iceland.

We investigated the frequency, cause and location of injuries in Icelandic elite soccer in 1991. The incidence of injuries for the individual player was 34.8 +/- 5.7 per 1000 game-hours and 5.9 +/- 1.1 per 1000 practice-hours. The most common types of injuries were muscle strains (29%), ligament sprains (22%), contusions (20%), and other injuries (29%). The frequency of reinjury was markedly high, where 44% of the strains and 58% of the sprains were registered as reinjuries. Strains occurred mainly during sprinting, sprains by tackling, and contusion during other contact. Significantly more injuries occurred on artificial turf than on grass or gravel in correlation to number of hours in games and practices. Teams who had the longest pre-season preparation period obtained significantly fewer injuries during the season.

A model to assess survival mechanisms of parasites in a genetically defined host system.

We examined a host system (peromyscus maniculatus) in which a single autosomal gene controls susceptibility or resistance to infection by the cestode parasite Hymenolepis citelli. Parasite deaths of both primary and secondary (challenge) infections were examined, using a probabilistic model, to see if deaths were random and uncorrelated within each genotype. Within susceptible hosts, post-patent survival of primary worms was not random and heterogeneity was due to among-host effects rather than parasite-age effects, suggesting a second genetic or immunological process. Secondary infections in susceptible hosts appear to be lost randomly, independent of primary infection age or burden. The loss rate is similar to that for primary worms. The lack of correlation or alteration in (susceptible) host response to primary and secondary infections suggests that the latter are eliminated by a process that differs from that acting on primary worms. In resistant hosts, parasite survival rates suggest that the immunological process elicited by the primary infection also acts to eliminate the secondary infection more rapidly. Suggestions are made for improving experimental methods when dealing with mixed genotype populations. Experiments should permit direct estimation of genotype frequency and of parasite death rates within each genotype. This separation of host type is particularly important when studying correlation of successive worm burdens since any host or treatment mixture (genotype, age, sex, size or infection dose) may induce correlations that could be mistakenly interpreted.

Rheumatic diseases in an Icelandic family. Clinical and immunological survey.

We have studied 192 members of a highly inbred Icelandic family with clustering of rheumatic diseases. Twelve consanguineous marriages are known in the family and 54 of 65 surviving offsprings of these (inbred group) were traced. Thirty-nine family members were affected by rheumatic diseases; 18 of them belonged to the inbred group. Eleven of 20 family members with rheumatoid arthritis (RA) came from the same inbred group. Eleven of the inbred group had a positive Rose-Waaler test for rheumatoid factor (RF) and the inbred group had significantly higher serum levels of IgG and IgM than an age and sex matched group from the family. Serum IgM RF was significantly associated with the age of the family members, but IgA RF and IgG RF did not show any such association. The possible role of recessive genes in the rheumatic diseases, as well as the inbreeding effect regarding certain extended HLA-complotypes is discussed.

Gene organization of haplotypes expressing two different C4A allotypes.

The gene organization of C4 haplotypes expressing two different C4A allotypes with a C4B null allele (C4A3A2BQ0 and C4A3A6BQO) was studied using Southern blot analysis with cDNA probes and restriction enzymes which give C4A and C4B locus-specific restriction fragments. These haplotypes were shown to have both a C4A and a C4B locus present, suggesting that the C4B locus expresses a C4A protein. The finding of a 21-OH A and a 21-OH B gene on the C4A3A6BQO haplotype further suggests that this haplotype has the common gene organization C4A, 21-OH A, C4B, 21-OH B. A model explaining C4 null alleles on haplotypes found to have two C4 loci is presented.

Molecular identification of hybrids between the two largest whale species, the blue whale (Balaenoptera musculus) and the fin whale (B. physalus).

Three anomalous balaenopterid whales, one pregnant female and two sterile males, were investigated by applying molecular approaches in order to establish their identity. The analysis showed that the whales were species hybrids between the blue and the fin whales. The female and one of the males had a blue whale mother and a fin whale father. The other male had a fin whale mother and a blue whale father. The difference between the mitochondrial cytochrome b gene of the two species suggests that they separated greater than or equal to 3.5 million years ago. The sequences of the mitochondrial control region of the blue and the fin whales differ by 7%. The difference in the mtDNA control region between three blue whale mtDNA haplotypes was less than or equal to 1%, about one tenth of the difference between the two species.