Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome

Summary Linkage data, using the polymorphic markers 52A (DXS51), F9, 4D-8(DXS98), and St14(DXS52), are presented from 14 fragile X pedigrees and from 7 normal pedigrees derived from the collection of the Centre d'Étude du Polymorphisme Humaine. A multipoint linkage analysis indicates that the most probable order of these four loci in normal families is DXS51-F9-DXS98-DXS52. Recombination frequencies ( ) corresponding to maximum LOD scores ( ) were obtained by two-point linkage analysis for a nuber of linkage groups, including: DXS51-F9 ( =5.94, =0.03), F9-DXS98 ( =0.51, =0.26), F9-DXS52 ( =0.84, =0.27), and DXS98-DXS52 ( =0.32, =0.20). A multipoint linkage analysis of these loci, including the fragile X locus, was also performed for the fragile X population and the data support the relative order (DSX51, F9, DXS98)-FRAXA-DXS52. Recombination frequencies and maximum LOD scores, which again were derived from two-point linkage analyses, were obtained for the linkage groups DXS51-F9 ( =9.96, =0) and F9-DXS52 ( =0.07, =0.45), as well as for the groups DXS51-FRAXA ( =2.42, =0.15), F9-FRAXA ( =1.30, =0.18), DXS98-FRAXA ( =0.05 =0.36), and DXS52-FRAXA ( =2.42 =0.15). The linkage data was further tested for the presence of genetic heterogeneity both within and between the fragile X and normal families for the intervals DXS51-F9, F9-DXS52, F9-FRAXA, and DXS52-FRAXA using a modification of the A test. Except for the interval F9-FRAXA (P<0.10) there was no evidence of genetic heterogeneity for each of the various linkage groups examined. The heterogeneity detected for the interval F9-FRAXA, however, was most likely due to one family (Fx-28) that displayed very tight linkage between these two loci.     

Spondyloepiphyseal dysplasia tarda: linkage with genetic markers from the distal short arm of the X chromosome

Summary A linkage study of six families with spondyloepiphyseal dysplasia tarda (SEDL) has been performed. A linkage to site DXS41 ( =0.08; =3.07) and DXS92 ( =0.05; =2.95) has been established. We propose, that the SEDL locus lies on the distal part of the short arm of the X chromosome.     

Evidence for linkage of the gene causing familial Mediterranean fever to chromosome 17q in non-Ashkenazi Jewish families: second locus or type I error?

Familial Mediterranean fever (FMF) is an autosomal recessive disorder of unknown pathogenesis, characterized by recurrent, selflimited attacks of fever with synovitis, peritonitis, or pleurisy. Using DNAs from affected Israeli families, we have recently mapped the gene causing FMF (designated MEF) to the short arm of chromosome 16, with two-point lod scores in excess of 20. In this report we consider the possibility of a second FMF susceptibility locus. Before discovering linkage to markers on chromosome 16, we had found suggestive evidence for linkage to chromosome 17q, with the following maximal two-point lod scores: D17S74 (pCMM86), = 2.47, ( = 0.20); D17S40 (pLEW101), = 2.15( = 0.15); D17S35 (CRI-pP3-1), = 1.78 ( = 0.15); D17S46 (pLEW108), = 1.69 ( = 0.18), D17S254, = 2.30 ( = 0.20). Moreover, multipoint linkage analysis using D17S74 and D17S40 as fixed loci gave = 3.27 approximately 10 centimorgans (cM) telomeric to D17S40. Data with the chromosome 17 markers alone in our families suggested locus heterogeneity. Nevertheless, our families were not separable into complementary subsets showing linkage either to chromosome 16 or to chromosome 17. We also examined the possibility that the positive lod scores for chromosome 17 might reflect a secondary, modifying locus. By several measures of disease severity, families with positive lod scores for chromosome 17 loci had no worse disease than those with negative lod scores for these loci. We conclude that chromosome 17 does not encode a major FMF susceptibility gene for some of the families, nor does it encode a disease-modifying gene. Rather, it would appear that linkage to chromosome 17 is a false positive (type I) error. These results reemphasize the fact that a lod score of 3.0 corresponds to a posterior probability of linkage of 95%, with an attendant 1 in 20 chance of observing a false positive.     

Estimating the Recombination frequency for the PTC-Kell linkage

Summary Two data sets are analyzed for linkage between the PTC and Kell blood group loci. The original report of close linkage for these loci was that of Conneally et al. (1976), where the maximum likelihood estimate of was 0.05. These two new data sets give a combined maximum likelihood estimate of _m=f =0.28. Estimating the recombination frequency for the sexes separately gave _m =0.29, _f =0.23. The combined maximum likelihood estimate over all published data sets including this report is _m=f =0.14, _max=8.94. There is statistically significant evidence of heterogeneity among the published studies.     

Likely linkage: Inv with Jk

Summary In a data base consisting of 1665 pairs of loci linkage between Inv and Jk is significant . Recombination is nearly the same in the two sexes . The reason why this linkage was not noticed earlier is discussed.     

Relationship between cardiac output and oxygen uptake at the onset of exercise

The purpose of the present study was to assess the relationship between the rapidity of increased gas exchange (i.e. oxygen uptake ) and increased cardiac output ( ) during the transient phase following the onset of exercise. Five healthy male subjects performed multiple rest-exercise or light exercise (25 W)-exercise transitions on an electrically braked ergometer at exercise intensities of 50, 75, or 100 W for 6 min, respectively. Each transition was performed at least eight times for each load in random order. The was obtained by a breath-by-breath method, and was measured by an impedance method during normal breathing, using an ensemble average. On transitions from rest to exercise, rapidly increased during phase I with time constants of 6.8–7.3 s. The also showed a similar rapid increment with time constants of 6.0–6.8 s with an apparent increase in stroke volume (SV). In this phase I, increased to about 29.7%–34.1% of the steady-state value and increased to about 58.3%–87.0%. Thereafter, some 20 s after the onset of exercise a mono-exponential increase to steady-state occurred both in and with time constants of 26.7–32.3 and 23.7–34.4 s, respectively. The insignificant difference between and time constants in phase I and the abrupt increase in both and SV at the onset of exercise from rest provided further evidence for a cardiodynamic contribution to following the onset of exercise from rest.     

Effects of root temperature on uptake of nitrate and ammonium ions by barley grown in flowing-solution culture

Summary Barley plants (Hordeum vulgare L.) grown from seed for 28 days in flowing solution culture were subjected to different root temperatures (3, 5, 7, 9, 11, 13, 17, 25°C) for 14 days with a common air temperature of 25/15°C (day/night). Uptake of NH₄ and NO₃ ions was monitored separately and continuously from solutions maintained at 10 M NH₄NO₃ and pH 6.0. Effects of root temperature on unit absorption rate , flux and inflow were compared. After 5 days , and increased with temperature over the range 3–11°C for NH₄ ions and over the range 3–13°C for NO₃ ions, with little change for either ion above these temperatures. Q₁₀ temperature coefficients for NH₄ ions (3–13°C) were 1.9, 1.7 and 1.6 for , and respectively, the corresponding values for NO₃ ions being 5.0, 4.5 and 4.6. For both ions, , and changed with time as did their temperature dependence over the range 3–25°C, suggesting that rates of ontogenetic development and the extent of adaptation to temperature may have varied among treatments.     

Estimation of surface charges in some biological membranes

Summary The resting membrane potential data existing in the literature for the giant axon of the squid, frog muscle and barnacle muscle have been analyzed from the standpoint of the theory of membrane potential due to Kobatake and co-workers. The average values derived for the effective charge density (where is a constant, , and represents the fraction of counterions that are free, and is the stoichiometric charge density in the membrane) present on the different biomembranes existing in their normal ionic environment are 0.3, 0.325 and 0.17 M for the squid axon, frog and barnacle muscles, respectively. On the assumption that the values of are 0.4 and 0.2 for nerve and muscle membranes, respectively, values of 0.75, 1.62 and 0.85 M have been derived for the stoichiometric charge density present in the respective biological membranes. These correspond to 1 negative charge per 222, 103 and 195 Å of the membrane area of the squid axon, frog and barnacle muscles, respectively.     

Respiratory responses of elite oarsmen, former oarsmen, and highly trained non-rowers during rowing, cycling and running

The position of the body and use of the respiratory muscles in the act of rowing may limit ventilation and thereby reduce maximal aerobic power relative to that achieved in cycling or running, in spite of the greater muscle mass involved in rowing. This hypothesis was investigated for three groups of male subjects: nine elite senior oarsmen, eight former senior oarsmen and eight highly trained athletes unskilled in rowing. The subjects performed graded exercise to maximal effort on a rowing ergometer, cycle ergometer and treadmill while respiratory minute volume and oxygen consumption were monitored continuously. The VE at a given during intense submaximal exercise (greater than 75% of maximal ) was not significantly lower in rowing compared with that in cycling and treadmill running for any group, which would suggest that submaximal rowing does not restrict ventilation. At maximal effort, and for rowing were less than those for the other types of exercise in all the groups, although the differences were not statistically significant in the elite oarsmen. These data are consistent with a ventilatory limitation to maximal performance in rowing that may have been partly overcome by training in the elite oarsmen. Alternatively, a lower maximal VE in rowing might have been an effect rather than a cause of a lower maximal if maximal was limited by the lower rate of muscle activation in rowing.     

Multipoint linkage analysis of the short arm of the human X chromosome in families with X-linked muscular dystrophy

Summary Sixteen three generation families from the West of Scotland with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) have been studied using the Xg blood group and seven cloned DNA sequences which recognise DNA polymorphisms on the short arm of the X chromosome (Xp). Linkage has been established between DMD and probe 754 with a maximum lod score () of 4.47 at a recombination fraction ( ) of 0.04. DMD has also been linked to probe 99-6 (=3.75, =0.03). Combining the data in this study with that of previously published work has established linkage between DMD and L1.28 (=4.42, =0.17) and altered the linkage estimate between BMD and L1.28 (=3.50, =0.22).An approximate order for the loci has been deduced by the study of recombinant chromosomes in phase known families informative for three or more loci. The proposed order is centromere-L1.28-754-DMD/BMD-99-6-D2-782-Xg. These results conclusively map both DMD and BMD to the central region of Xp and add weight to the original suggestion that they may be allelic.     

Breeding success, nestling diet and parental care in the White-backed WoodpeckerDendrocopos leucotos

In western Norway, pairs of White-backed Woodpecker breeding in coastal areas (<2 km from the sea) started egg laying earlier than pairs in inland areas (2–15 km from the sea). Laying was earlier in years when the ambient temperature was higher during the pre-laying period. About half of 69 pairs studied started laying within the period 25–30 April over the 10 study years. Clutch size ( = 4.0 eggs) and breeding success values (fledglings per egg; = 0.63) did not differ between years. The mean number of fledglings per nest was 2.4. The mean body mass of fledglings differed between years and were negatively correlated with the laying date. Fledgling mass differed between sexes (males = 87.8g, females = 84.2g), and both sexes were heavier in coastal than in inland areas. The mean hourly feeding rate of nestlings increased with nestling age, but feeding rate per nestling did not vary with nestling number. The nestling food was mainly comprised by wood-living beetle larvae ( = 72% by dry mass). It is suggested that breeding success is related to territorial quality, which, in turn, strongly influences female quality.

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Zusammenfassung In Westnorwegen beginnen Weißrückenspechte, die an der Küste brüten, eher mit der Eiablage als Paare im Inland (>2 km von der Küsten entfernt). Höhere Lufttemperaturen in der Vorlegezeit begünstigten frühere Eiablage. Mehr als die Hälfte der 69 untersuchten Paare begannen innerhalb von 10 Jahren zwischen 25. und 30. April mit der Eiablage. Gelegegröße ( = 4,0 Eier) und Bruterfolg (flügge Junge pro Ei; = 0,63) unterschieden sich nicht in einzelnen Jahren. Pro Nest flogen 2,4 Junge aus. Die mittlere Körpermasse der flüggen Jungvögel war mit dem Datum der Eiablage negativ korreliert. Flügge Männchen waren etwas schwerer als gleichalte Weibchen ( 87,9, 84,2 g); beide Geschlechter waren in Küstengebieten schwerer als im Inland. Die mittlere Fütterungsrate pro Stunde stieg mit dem Alter der Nestlinge, veränderte sich aber nicht mit der Zahl der Nestlinge. Die Nestlingsnahrung bestand vor allem aus holzbewohnenden Käferlarven ( = 72% der Trockenmasse). Vermutlich hängt der Bruterfolg mit der Qualität des Brutreviers zusammen, die wiederum vor allem die Kondition des Weibchens bestimmt.

     

Breathing pattern and growth: comparative aspects

Summary The resting oxygen consumption and breathing pattern of nine newborn and adult species (ranging in body size from mouse to human) have been compared on the basis of data collected from the literature. Minute ventilation is similarly linked to at both ages, the percent of extracted as O₂ about 2.2. Tidal volume/kg is an interspecies constant in newborns and adults, approximately 8 ml/kg. Breathing frequency decreases with the increase in size in a different way at the two ages: large species have newborns breathing at rates 2–3 times above the corresponding adults' values, while in the small species newborns and adults breathe at almost the same rate. Therefore the newborns of the smallest species have both and below the expected values, implying a greater inability to cope with the external demands than newborns of larger species. Several considerations indicate that in the smallest newborns the mechanical properties of the respiratory system could be a constraint to resting ventilations larger than observed. It is therefore possible that their low is the cause, and not the effect, of the relatively small .     

Influence of lifting technique on perceptual and cardiovascular responses to submaximal repetitive lifting

Oxygen consumption ( O₂), heart rate, ventilation and central rating of perceived exertion (RPE) in repetitive lifting while executing squat and stoop techniques were investigated in ten male forestry workers. In all five mass/frequency combinations studied, O₂ was significantly higher for the squat than for the stoop technique. No differences were found in RPE between the techniques. The O₂ and RPE recordings were also related to those obtained during maximal repetitive lifting (same lifting technique) and maximal treadmill running. The O₂ expressed as a percentage of that obtained during maximal repetitive lifting with the same lifting technique was defined as relative aerobic intensity (% O_{2max, lifting}). The % O_{2max, lifting} was not significantly different between the techniques except for the lowest mass lifted (1 kg). This study therefore would support the hypothesis that RPE is more closely related to % O_{2max, lifting} than to absolute aerobic intensity. Related to maximal treadmill running, it was demonstrated for both lifting techniques that relative RPE (percentage of the RPE during maximal running) was more accurate than relative O₂ (percentage of maximal O₂ during maximal running) for determining the % O_{2max, lifting} in repetitive lifting. The study showed that the higher O₂ during squat. lifting compared to stoop lifting was caused by the O₂ expended in lifting and lowering the body rather than the O₂ expended lifting and lowering the external mass. It was concluded that the stoop technique was not superior to the squat technique in terms of central RPE. Based on % O_{2max, lifting}, there may be a rationale for choosing the stoop technique during repetitive lifting with light masses, but not with heavy masses.     

Skeletal muscle [(V)\dot]O2 \dot V_{O_2 } in rat and lemming: Effect of blood flow rate

Summary The rate of oxygen consumption ( ) by skeletal muscle was investigated in isolated perfused hindlimbs of laboratory rats and lemmings (Lemmus). In both species, increased in proportion to blood flow rate, even at flow rates 4–5 times above resting level. The slope of the line relating to skeletal muscle blood flow was significantly greater in the lemming than in the rat. This may be related to the inverse relationship between body weight and metabolic rate. These data support the hypothesis that in small animals a dependent relationship exists between blood flow and skeletal muscle .     

On the accuracy of some mark-recapture estimators

Summary The behaviour of the mark-recapture estimators of Petersen, Bailey (triple catch) and Jolly and Seber are examined theoretically and empirically by means of simulation techniques. The correlation between the parameter and its associated variance is shown to be significant for all the estimators. This correlation makes the estimated variance an insensitive measure of the accuracy of the estimate except at very high sampling intensities. Such sampling intensities are rarely achieved in experimental work and so the method of mark-recapture must be considered of very limited use. At the sampling intensities necessary to give a coefficient of variation of less than 0.05 it does not seem likely that the correlation between and its variance will produce serious underestimation but the minimum confidence limits are recommended.     

Body temperatures during rest and exercise in residents and sojourners in hot climate

Rectal (T_re), mean skin temperature ( _sk) and sweating rate ( ) were measured in 4 residents of temperate climate under acute moderate heat exposure (designated EE in such an experimental situation), after 3 weeks in India (designated as EI) and in 8 Indian residents (designated as II) both at rest and during submaximal exercises at 2 different intensities. At rest, T_re is higher in EI (37.6°C) than in EE (36.8°C, P<0.01) and reaches 37.8°C in II. At the end of exercise, the increment in T_re seems to depend on work load only and to be independent of thermal environment; S follows a similar pattern in the 3 groups of subjects: _sk is altered neither by exercise nor acclimatization. Under chronic heat exposure compared to acute conditions: (1) identical is achieved with higher T_re and similar _sk so that the linear relationships vs T_re is shifted to the right. (2) the T_re — _sk difference is greater at rest and during exercise: hence, skin blood flow, calculated from heat balance equation diminishes. In hot climate, a rise in T_re seems to be an adaptive response which allows the body to reduce skin blood flow.     

Aerobic and anaerobic contribution to Wingate test performance in sprint and middle-distance runners

We investigated the aerobic and anaerobic contributions to performance during the Wingate test in sprint and middle-distance runners and whether they were related to the peak aerobic and anaerobic performances determined by two commonly used tests: the force-velocity test and an incremental aerobic exercise test. A group of 14 male competitive runners participated: 7 sprinters, aged 20.7 (SEM 1.3) years, competing in 50, 100 and 200-m events and 7 middle-distance runners, aged 20.0 (SEM 1.0) years, competing in 800, 1,000 and 1,500 m-events. The oxygen uptake ( ) was recorded breath-by-breath during the test (30 s) and during the first 20 s of recovery. Blood samples for venous plasma lactate concentrations were drawn at rest before the start of the test and during the 20-min recovery period. During the Wingate test mean power ( ) was determined and three values of mechanical efficiency, one individual and two arbitrary, 16% and 25%, were used to calculate the contributions of work by aerobic ( _{aer,ind,16%,25%}) and anaerobic ( _{an,ind,16%,25%}) processes. Peak anaerobic power ( _an,peak) was estimated by the force-velocity test and maximal aerobic energy expenditure ( _aer,peak) was determined during an incremental aerobic exercise test. During the Wingate test, the middle-distance runners had a significantly greater than the sprinters (P < 0.001), who had significantly greater venous plasma lactate concentrations (P < 0.001). Moreover, _{aer,ind,16%,25%} were also significantly higher (P < 0.05) in the middle-distance runners [ _aer,ind 45 (SEM 4) % vs 28 (SEM 2) %; _aer,16% 30 (SEM 3) % vs 19 (SEM 2) %; _aer,25% 46 (SEM 3) % vs 29 (SEM 2)%]; _{an,ind,16%,25%} in the sprint runners (P < 0.05) [ _an,ind 72 (SEM 3) % vs 55 (SEM 4) %; _an,16% 81 (SEM 2) % vs 70 (SEM 3) %; _an,25% 71 (SEM 2) % vs 54 (SEM 3) %]. The _aer,ind/ _aer,peak and × _an,ind/ _an,peak ratios, however, were not significantly different between the two groups of athletes. These results would indicate that the sprinters and middle-distance runners used preferentially a metabolic system according to their speciality. Nevertheless, under the conditions of its experiment, they seemed to rely on the same percentage of both peak anaerobic and peak aerobic performance for a given exercise task.     

Reciprocal inhibition of human motoneurons with different firing frequencies

A study was made of the effect of reciprocal inhibition on individual firing motoneurons in the extensor carpi ulnaris and soleus muscle in human subjects. Peristimulus histograms (PSH) were plotted at different average frequency of motoneuron firing ( ) and the change in duration of interspike intervals (ISI) was analyzed. For reciprocal inhibition, as for other types of inhibition, is a factor in the effectiveness of motoneuron inhibition. The duration of inhibition apparent in the PSH, the sizes of zones of inhibition effectiveness in the ISIs and lengthening of the intervals are dependent on . For all motoneurons, the low range is most favorable for effective inhibition. The dependence of effectiveness of a volley on the time of its arrival within the ISI is also analyzed.Institute for Problems of Information Transmission, Russian Academy of Sciences, Moscow. Translated from Neirofiziologiya, Vol. 24, No. 6, pp. 643–653, November–December, 1992.     

Activity and oxygen consumption during hypoxic exposure in high altitude and lowland sceloporine lizards

Summary Resting rates of O₂ consumption against , exercise endurance times and during recovery from vigorous exercise were measured inSceloporus occidentalis captured near sea level and inS. graciosus captured above 2850 m. Oxygen consumption against was also measured inS. occidentalis captured above 2850 m. When was recorded continuously, as ambient was slowly reduced from 155 Torr, it became directly dependent upon ambient between 110 and 120 Torr. The critical for the high altitude lizards was lower than that for the lowland lizards, which enabled the former to maintain relatively higher 's when ambient was reduced below 120 Torr. The high altitude lizards also had significantly greater endurance when stimulated to exercise at 1600 m ( 130 Torr). Both the higher under hypoxia and the greater endurance roughly parallel a significantly greater maximum in the high altitude lizards. At a simulated altitude of 3600 m ( 100 Torr), maximum and rate of recovery of the O₂ debt calculated from post active were significantly reduced in the lowland but not the high altitude lizards. The effects of simulated altitude conditions on the lowland but not the mountaine animals indicate adaptations to altitude in these sceloporine lizards. We did not find any consistent relationship between organ/body weight ratios or hematocrit and our measures of endurance or the altitude at which the lizards were captured.     

Dynamics of cardiorespiratory function in Standardbred horses during different intensities of constant-load exercise

Summary Six Standardbred horses were used to evaluate the time course of pulmonary gas exchange, ventilation, heart rate (HR) and acid base balance during different intensities of constant-load treadmill exercise. Horses were exercised at approximately 50%, 75% and 100% maximum oxygen uptake ( max) for 5 min and measurements taken every 30 s throughout exercise. At all work rates, the minute ventilation, respiratory frequency and tidal volume reached steady state values by 60 s of exercise. At 100% max, the oxygen consumption ( ) increased to mean values of approximately 130 ml/kg·min, which represents a 40-fold increase above resting . At the low and moderate work rates, showed no significant change from 30 s to 300 s of exercise. At the high work rate, the mean at 30 s was 80% of the value at 300 s. The HR showed no significant change over time at the moderate work rate but differing responses at the low and high work rates. At the low work rate, the mean HR decreased from 188 beats/min at 30 s to 172 beats/min at 300 s exercise, whereas at the high work rate the mean HR increased from 204 beats/min at 30 s to 221 beats/min at 300 s exercise. No changes in acid base status occurred during exercise at the low work rate. At the moderate work rate, a mild metabolic acidosis occurred which was nonprogressive with time, whereas the high work rate resulted in a progressive metabolic acidosis with a base deficit of 16 mmol/l by 300 s exercise. It is concluded that the kinetics of gas exchange during exercise are more rapid in the horse than in man, despite the relatively greater change in in the horse when going from rest to high intensity exercise.Symbols and abbreviations E minute ventilation - V _T tidal volume - oxygen uptake - carbon dioxide output - oxygen pulse - ventilatory equivalent for oxygen - ventilatory equivalent for carbon dioxide - R respiratory exchange ratio - HR heart rate - SBC standard bicarbonate - STPD standard temperature and pressure dry - BTPS body temperature and pressure saturated - arterial oxygen content - arteriovenous oxygen content difference - Rf respiratory frequency