Single Autosomal Gene Research Articles

The Distribution of Curvature of Little Finger (Clinodactyly) among the Idoma People of Benue State, Nigeria

Background: A bilateral malformation known as Clinodactyly, or curvature of the little finger in the radio-ulnar plane, causes the finger to be stunted and curved, or inclined, towards the ring finger. It is known to be a morphogenetic trait. Reports say that Clinodactyly seems to be passed on by a single autosomal dominant gene. There is paucity of information on curvature of the little finger in the Idoma tribe of Benue State, Nigeria; hence, this study was aimed at determining the distribution of curvature of the little finger in the study population. Materials and Methods: The study was descriptive and cross-sectional in design with 401 participants recruited randomly following a multi-staged sampling method. Results and Discussion: The most frequent socio-demographic characteristics were age category 33-47yrs with 213(53.1%), male gender with 223(55.6%), Tertiary education with 239(59.6%), Married/Co-habiting 220(54.9%), and Christianity 286(71.3%). The significant socio-demographic characteristic among participants were educational level (X2 =14.090, p=0.003) and marital status (X2 =10.901, p=0.05). The proportion of participants with a curved little finger was 18.9%. In the population a large portion of them had straight little finger. Conclusion(s): The proportion of participants with a curved little finger was 18.9%. In the population a large portion of them had straight little finger. The study showed that less than a third of the sampled population had a curved little finger and the remaining two-third a straight little finger. The ratio of curved to straight little finger was 1:4.

Severe hypercholesterolemia in a patient with very low albumin and normal renal function

A 20-year-old male presented with severe elevation in low-density lipoprotein cholesterol (LDL-C). Initial genetic testing for familial hypercholesterolemia was negative. Patient also had low albumin, and further genetic testing showed homozygous variants in the ALB gene, suggesting congenital analbuminemia (CAA) causing severe hyperlipidemia. CAA is an autosomal recessive disorder with incidence of about 1:1,000,000. The gene for albumin is a single autosomal gene, and pathological variants that affect splicing lead to premature stop, nonsense variants, and deletions that result in a defect in albumin synthesis with CAA. CAA can be fatal in the prenatal period and cause infections in early childhood. CAA is tolerated better in adulthood because of compensatory increase in other plasma proteins. Plasma lipoproteins also increase, and CAA can cause gross hyperlipidemia with severe elevations in LDL-C and hypercholesterolemia. Genetic examination of ALB is mandatory to establish the diagnosis. Early diagnosis may be important to initiate lipid-lowering treatments to avoid premature coronary artery disease.

Genetic analysis and molecular detection of resistance to chlorpyrifos mediated by the A216S substitution in acetylcholinesterase-1 in the plant bug Apolygus lucorum.

The green plant bug Apolygus lucorum is a major pest of Bacillus thuringiensis cotton in China. Previously, we reported that chlorpyrifos resistance in a laboratory‐selected strain of A. lucorum (BZ‐R) is associated with the homozygosis of an allele in the ace‐1 gene encoding an alanine to serine substitution at position 216 of acetylcholinesterase‐1. Here we describe the results of crosses between the resistant BZ‐R strain (41‐fold to chlorpyrifos) and the unselected susceptible BZ‐S strain homozygous for the wild type alanine allele at position 216. Resistance to chlorpyrifos was inherited as a semi‐dominant trait mainly controlled by a single autosomal gene and co‐segregates strongly but not completely with the serine substitution in ace‐1. Synergism bioassays and enzyme assays showed that minor contributions to resistance are also made by enhanced cytochrome P450 and carboxylesterase activities. A survey of 25 field populations from five Chinese provinces showed strong positive correlations between 50% lethal concentration against chlorpyrifos and S216 allele and genotype frequencies, although the most tolerant populations still only show 40%–50% S216 allele frequencies. The results above provide important information for designing effective resistance monitoring and management strategies for A. lucorum in China.

Inheritance and fitness costs of Cry1A.105 resistance in two strains of Spodoptera frugiperda (J.E. Smith)

Cry1A.105 is a Bacillus thuringiensis (Bt) protein expressed in many Bt corn hybrids for controlling moth pests including the fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith). The objective of this study was to compare the inheritance and fitness costs of two Cry1A.105-resistant FAW strains (RR32 and RR67) from Florida, U.S. To assess inheritance of the resistance, larval mortality of one susceptible strain (SS), RR32, RR67, and eight FAW strains generated from various genetic crosses was assayed on Cry1A.105-treated diet and Cry1A.105 corn leaf tissues. In the fitness cost study, survival, growth, development, and fecundity of SS, RR32, RR67, and two F1 heterozygous-resistant FAW strains were evaluated on non-Bt corn leaf tissue. The Cry1A.105 resistance in both RR32 and RR67 was likely inherited as a single autosomal gene with no fitness costs. The dominance levels differed between the two strains and varied from incompletely recessive to incompletely dominant, depending on Cry1A.105 concentrations and assay materials. The results of this study indicate a relatively high risk of resistance development to single-gene Cry1A.105 corn in FAW. Together with published data, the results also show that non-recessive resistance and lack of fitness costs in resistance to Bt crops are not uncommon, which provides a cautionary evidence against the assumption that resistance is recessive in an resistance management plan for Bt crops.

Pcarrier: Individual and family distributions of a susceptibility gene for breast and ovarian cancer based on family history.

e13005 Background: Most of the BRCA1/2 and PALB2 analyses performed in patients with a personal and familial history (FH) of breast/ovarian cancer are negative. In this context, there is no targeted analysis available to identify relatives at high risk (carrier of the causal hypothetical mutated gene). Thus, the recommendations of surveillance to all relatives are based only on the FH of cancer. At the Institut Curie we assess the degree of severity of the FH by calculating the probability of carrying a single autosomal dominant susceptibility gene without taking into account genotyping results but using the LINKAGE software with the parameters of the Claus-Easton model (1993). This reliable but old tool has a slow console interactive interface (roughly 15 min of clinicians time for each assessed family). Methods: We rewrite the model as a Bayesian network combining Mendelian genetics with classical survival analysis. All probabilistic computations are performed through belief propagation (sum-product algorithm) over real numbers or polynomials. The programming language is C++. Results: pCarrier is a modern and efficient implementation of the Claus-Easton model for clinicians with the following features: 1) fast non-interactive command line ( < 1s to process a previously registered family) combined with a graphical user-friendly interface; 2) computations dealing with monozygotic twins or loops without any human intervention (ex: loop breaking); 3) choice between the original discretized model (individual FH into 14 classes) and its continuous version (piecewise constant hazard); 4) marginal individual carrier distribution for all individuals in the pedigree; 5) joint distribution of the number of carriers among any group of individuals (ex: in the entire family, among the living only). Conclusions: pCarrier is experimented since January 2017 in the Institut Curie as a replacement of the existing tool and appears so far to be dramatically faster and easier to use for the clinicians, highly reliable (consistence with the existing tool), and able to provide new useful decision-making probabilities using the distribution of the number of carriers.

Hormonal sex reversal in red tilapia (Oreochromis niloticus and Oreochromis mossambicus) and inheritance of body colour in O. mossambicus and red tilapia: implications for commercial farming

The present investigation was conducted with a view to produce a female-free population and to test the heredity of body colour in tilapia. In this study, 6-day-old red tilapia were fed diets incorporated with 0, 25, 50, 75 and 100 mg/kg diet of a synthetic androgen, 17α-methyltestosterone (17α-MT), for 30 days. Administration was followed by 120 days of rearing in nylon hapas where hormone-free diet was given. At the end of the 120-day rearing, 17α-MT at 50 ppm induced 100% sex reversal, whereas 25, 75 and 100 mg/kg resulted in incomplete sex reversal. Immersion of newly hatched red tilapia fry in an aqueous solution of 17α-MT at 200 μg/L for 1 h produced 73% males; however, when given to 2-day-old fry, it yielded 78% males. The results indicate that oral administration of 17α-MT is more effective than treatment by immersion to produce male dominant red tilapia populations. Treatment of red tilapia with the androgen did not indicate any definite trend in the gonado-somatic index of both males and females. The results of progeny testing indicate that red tilapia does not belong to either XX-XY or WZ-ZZ sex determination systems, the two most common sex determination systems that exist in fish. When mating, Oreochromis mossambica (black tilapia) and red hybrid tilapia produced F1 progeny with a brown colour, the intermediate colour between the two parental body colours. When F1 hybrids were interbred, the three phenotypes got separated in the F2 generation with a 1 black/2 brown/1 red phenotypic ratio as expected of a single autosomal gene with incomplete dominant gene action. The importance of monosex male red tilapia farming and body colour inheritance is also discussed.

Epileptic encephalopathies: new genes and new pathways.

Epileptic encephalopathies represent a group of devastating epileptic disorders that occur early in life and are often characterized by pharmaco-resistant epilepsy, persistent severe electroencephalographic abnormalities, and cognitive dysfunction or decline. Next generation sequencing technologies have increased the speed of gene discovery tremendously. Whereas ion channel genes were long considered to be the only significant group of genes implicated in the genetic epilepsies, a growing number of non-ion-channel genes are now being identified. As a subgroup of the genetically mediated epilepsies, epileptic encephalopathies are complex and heterogeneous disorders, making diagnosis and treatment decisions difficult. Recent exome sequencing data suggest that mutations causing epileptic encephalopathies are often sporadic, typically resulting from de novo dominant mutations in a single autosomal gene, although inherited autosomal recessive and X-linked forms also exist. In this review we provide a summary of the key features of several early- and mid-childhood onset epileptic encephalopathies including Ohtahara syndrome, Dravet syndrome, Infantile spasms and Lennox Gastaut syndrome. We review the recent next generation sequencing findings that may impact treatment choices. We also describe the use of conventional and newer anti-epileptic and hormonal medications in the various syndromes based on their genetic profile. At a biological level, developments in cellular reprogramming and genome editing represent a new direction in modeling these pediatric epilepsies and could be used in the development of novel and repurposed therapies.

Type I interferon signaling genes in recurrent major depression: increased expression detected by whole-blood RNA sequencing.

A study of genome-wide gene expression in major depressive disorder (MDD) was undertaken in a large population-based sample to determine whether altered expression levels of genes and pathways could provide insights into biological mechanisms that are relevant to this disorder. Gene expression studies have the potential to detect changes that may be due to differences in common or rare genomic sequence variation, environmental factors or their interaction. We recruited a European-ancestry sample of 463 individuals with recurrent MDD and 459 controls, obtained self-report and semi-structured interview data about psychiatric and medical history and other environmental variables, sequenced RNA from whole blood and genotyped a genome-wide panel of common SNPs. We used analytical methods to identify MDD-related genes and pathways using all of these sources of information. In analyses of association between MDD and expression levels of 13,857 single autosomal genes, accounting for multiple technical, physiological and environmental covariates, a significant excess of low p-values was observed, but there was no significant single-gene association after genome-wide correction. Pathway-based analyses of expression data detected significant association of MDD with increased expression of genes in the interferon α/β signaling pathway. This finding could not be explained by potentially confounding diseases and medications (including antidepressants) or by computationally-estimated proportions of white blood cell types. Although cause-effect relationships cannot be determined from these data, the results support the hypothesis that altered immune signaling plays a role in the pathogenesis, manifestation, and/or the persistence and progression of MDD.

Characteristics of Resistance to Bacillus thuringiensis Toxin Cry2Ab in a Strain of Helicoverpa punctigera (Lepidoptera: Noctuidae) Isolated From a Field Population

In 1996, the Australian cotton industry adopted Ingard that expresses the Bacillus thuringiensis (Bt) toxin gene cry1Ac and was planted at a cap of 30%. In 2004-2005, Bollgard II, which expresses cry1Ac and cry2Ab, replaced Ingard in Australia, and subsequently has made up >80% of the area planted to cotton, Gossypium hirsutum L. The Australian target species Helicoverpa armigera (Hübner) and Helicoverpa punctigera (Wallengren) are innately moderately tolerant to Bt toxins, but the absence of a history of insecticide resistance indicates that the latter species is less likely to develop resistance to Bt cotton. From 2002-2003 to 2006-2007, F2 screens were deployed to detect resistance to CrylAc or Cry2Ab in natural populations of H. punctigera. Alleles that conferred an advantage against CrylAc were not detected, but those that conferred resistance to Cry2Ab were present at a frequency of 0.0018 (n = 2,192 alleles). Importantly, the first isolation of Cry2Ab resistance in H. punctigera occurred before significant opportunities to develop resistance in response to Bollgard II. We established a colony (designated Hp4-13) consisting of homozygous resistant individuals and examined their characteristics through comparison with individuals from a Bt-susceptible laboratory colony. Through specific crosses and bioassays, we established that the resistance present in Hp4-13 is due to a single autosomal gene. The resistance is fully recessive. Homozygotes are able to survive a dose of Cry2Ab toxin that is 15 times the reported concentration in field grown Bollgard II in Australia (500 microg/ml) and are fully susceptible to Cry1Ac and to the Bt product DiPel. These characteristics are the same as those described for the first Cry2Ab resistant strain of H. armigera isolated from a field population in Australia.

Breeding Evidence for Conspecific Status ofGrammia phyllira(Drury, 1773) andGrammia oithona(Strecker, 1878) (Erebidae: Arctiinae), with Notes on Natural History and Conservation Status

It has long been suspected that Grammia oithona may be a form of G. phyllira, but concrete evidence has been lacking. The only obvious difference between G. oithona and G. phyllira is the presence of cream-colored scales outlining the veins of the forewing of G. oithona. A female G. oithona from Hampden County, Massachusetts, U.S.A., produced progeny consisting of 55 phyllira and 51 oithona. The following year a female G. phyllira from the same locality produced 33 phyllira and 40 oithona. Therefore the name oithona represents a wing pattern phenotype, not a species, at least in the population studied. Progeny of both wild females were bred in captivity, each cross consisting of a virgin female bred with a single male, with eight separate crosses producing offspring. The simplest, most parsimonious hypothesis consistent with the data from all eight crosses is that the wing pattern phenotype is inherited as a single autosomal gene with two alleles, a dominant phyllira allele and a recessive oithona allele; dominance may be incomplete in heterozygotes. Assuming G. phyllira and G. oithona to be conspecific across their composite range, the phyllira phenotype occurs with high frequency in most populations along the East Coast and in the Upper Midwest, and with low frequency in most populations to the west and south of this range. G. phyllira is of conservation concern in the northeastern U.S.A., where it has declined substantially during the past 50 to 100 years. The natural history of G. phyllira is typical of Grammia species, but its dependence on grassland and savanna habitat on dry, sandy soils is an important consideration in conservation and management efforts for this species.

Suri and huacaya alpaca breeding results in North America

The segregation of suri and huacaya fleece types in alpacas in the United States deviates from that expected from results of previously published studies from other regions. Suri × suri matings produced 278 huacaya and 1702 suri offspring. Suri × huacaya matings produced 89 huacaya and 56 suri offspring. Huacaya × huacaya matings produced 19,633 huacaya and 4 suri offspring. No linkage or other influence of sex was noted. These results are consistent with a single autosomal dominant gene controlling suri fleece production, with an additional relatively common genetic mechanism that can suppress the suri phenotype in some animals. These results are especially important in cases where the two fleece types are crossed with one another, as they result in a relative underproduction of suri fleeces.

Inheritance and stability of pyrethroid resistance in the cotton bollworm Helicoverpa armigera (Lepidoptera: Noctuidae) in Central Africa

The cotton bollworm Helicoverpa armigera (Hübner) has developed esterase-mediated resistance to pyrethroids in Central Africa. To gain a better understanding of how quickly this resistance can evolve, its genetic basis and stability were examined in a field-derived strain of H. armigera (474-fold resistant to cypermethrin). Genetic crosses between susceptible, resistant and F(1) hybrids indicated that resistance was inherited as a dominant trait (D(LD) = 0.86) and conferred by a single autosomal gene. The dominance of resistance decreased as the cypermethrin dose increased, so that resistance was incompletely dominant (D(ML) = 0.73) at the highest dose tested. Resistance (DL(50)) of the F(1) hybrid progeny significantly decreased over five generations in the absence of pyrethroid exposure. Rapid selection of resistance alleles due to dominance supports the ability of H. armigera to develop resistance to pyrethroids in Central Africa. However, associated fitness costs provide useful information for managing the evolution of resistance.

Apobec3 Encodes Rfv3 , a Gene Influencing Neutralizing Antibody Control of Retrovirus Infection

Recovery from Friend virus 3 (Rfv3) is a single autosomal gene encoding a resistance trait that influences retroviral neutralizing antibody responses and viremia. Despite extensive research for 30 years, the molecular identity of Rfv3 has remained elusive. Here, we demonstrate that Rfv3 is encoded by Apobec3. Apobec3 maps to the same chromosome region as Rfv3 and has broad inhibitory activity against retroviruses, including HIV. Not only did genetic inactivation of Apobec3 convert Rfv3-resistant mice to a susceptible phenotype, but Apobec3 was also found to be naturally disabled by aberrant messenger RNA splicing in Rfv3-susceptible strains. The link between Apobec3 and neutralizing antibody responses highlights an Apobec3-dependent mechanism of host protection that might extend to HIV and other human retroviral infections.

444. Embryonic survival in prolific ewes

Introduction: A significant proportion of potential lambs are lost (commonly 15–20%) between ovulation and birth. Little is currently known about factors associated with multiple birth capacity of the uterus which are essential to convert gains in ovulation rate to live lambs. The relationship between maternal uterine and hormonal environment as well as the heritability of embryonic survival (ES) in prolific ewes is investigated. Methods: Litter size (LS) from known ovulation rate (OR) records (n = 6393) collected over 16 years were assessed for heritability with ASREML analysis and to identify the pedigree of outliers. From this flock, closely related high ovulation rate ewes with significantly different litter sizes (High ES; OR2.6/LS2.4 v. Low ES; OR2.9/LS1.6) were selected. Uterine anatomy collected from Day 14 cyclic (n = 5 High and n = 5 Low ES) and Day 16 pregnant ewes (n = 14 high and n = 10 Low) as well as systemic concentrations of hormones indicative of uterine (activin-A, follistatin) and ovarian (inhibin-{α}, progesterone) function were compared. Results and Discussion: ASREML analysis reported ES to be a trait of low repeatability (r = 0.10) and even lower heritability (h2 = 0.04). However, pedigrees of outlier animals indicated a segregation pattern consistent with a single autosomal gene with a major effect on enhanced ES. No anatomical differences between high and low ES ewes were discerned. However, significant differences for circulating levels of activin-A (depressed), time of activin-A peak (earlier), follistatin (elevated), progesterone (early rise) and inhibin-{α} (depressed) concentrations were found around the time of oestrus in High v. Low ES ewes. Given the involvement of activin-A in injury-induced inflammation, these results suggest a role for the activin-follistatin system, possibly through increased residency of immune cells and cytokine activation, for increasing ES in prolific ewes. Acknowledgements; Norma Hudson and Stan Lun for progesterone and inhibin-{α} assays.

Resistance to <I>Bacillus thuringiensis</I> Toxin Cry2Ab in a Strain of <I>Helicoverpa armigera</I> (Lepidoptera: Noctuidae) in Australia

Transgenic cotton, Gossypium hirsutum L., expressing the crylAc and cry2Ab genes from Bacillus thuringiensis (Bt) Berliner variety kurstaki in a pyramid (Bollgard II) was widely planted for the first time in Australia during the 2004-2005 growing season. Before the first commercial Bollgard II crops, limited amounts of cotton expressing only the crylAc gene (Ingard) was grown for seven seasons. No field failures due to resistance to CrylAc toxin were observed during that period and a monitoring program indicated that the frequency of genes conferring high level resistance to the CrylAc toxin were rare in the major pest of cotton, Helicoverpa armigera (Htibner) (Lepidoptera: Noctuidae). Before the deployment of Bollgard II, an allele conferring resistance to Cry2Ab toxin was detected in field-collected H. armigera. We established a colony (designated SP15) consisting of homozygous resistant individuals and examined their characteristics through comparison with individuals from a Bt-susceptible laboratory colony (GR). Through specific crosses and bioassays, we established that the resistance present in SP15 was due to a single autosomal gene. The resistance was recessive. Homozygotes were highly resistant to Cry2Ab toxin, so much so, that we were unable to induce significant mortality at the maximum concentration of toxin available. Homozygotes also were unaffected when fed leaves of a cotton variety expressing the cry2Ab gene. Although cross-resistant to Cry2Aa toxin, SP15 was susceptible to CrylAc and to the Bt product DiPel.

Pleiotropic effects associated with an allele enabling the flea beetle Phyllotreta nemorum to use Barbarea vulgaris as a host plant

In the Danish region of Kvaerkeby, a mutation in an, as yet, unknown single autosomal gene has resulted in a dominant resistance (R-) allele in the flea beetle Phyllotreta nemorum L. (Coleoptera: Chrysomelidae: Alticinae). It enables the beetle to overcome the defences of Barbarea vulgaris ssp. arcuata (Opiz.) Simkovics G-type (Brassicaceae) and use it as a host plant. In this study, we investigated the pleiotropic effects associated with the presence of this particular R-allele in female P. nemorum. These females had the R-allele backcrossed into the genetic background of non-resistant beetles. The effects were investigated under both favourable and stressful conditions (cold shock). The presence of the R-allele in a non-resistant genetic background caused a very high mortality in resistant individuals during the early stages of development under both conditions, but it did not affect the adult life-history traits longevity, body size and fecundity, under both conditions. Regardless of temperature treatment, resistant females in general were found to lay significantly more eggs. Developmental stability, as measured by tibia length fluctuating asymmetry, was not correlated with overall developmental stress in this study.

Inheritance of proportionate dwarfism in Angus cattle

To determine the mode of inheritance of congenital proportionate dwarfism in Angus and Angus crossbred cattle, initially detected in two commercial beef herds in northern New South Wales. Matings of normal carrier sires to unrelated cows of diverse breeds, and of one carrier sire to his unaffected daughters. An unrelated Piedmontese bull was also mated to unaffected daughters of the carrier sires. Two carrier Angus bulls and nine unaffected daughters, all of whom were completely indistinguishable from normal animals, were purchased for controlled breeding studies under known nutritional and disease conditions. Affected and carrier individuals were examined for the presence of obvious chromosomal abnormalities. Angus dwarfism has been successfully reproduced under controlled experimental conditions over successive years using unrelated dams and is undoubtedly heritable. The high frequency of occurrence of affected individuals (23/61 = 0.38 +/- .06) among the progeny of matings of the Angus sires to unrelated females of diverse breeding is not compatible with recessive inheritance, because of the negligible frequency of proportionate dwarfism in the breeds of the dams. Both paternal and maternal transmission of the defect was demonstrated, so that imprinting in the strict sense of a gene that is only expressed when received from the male parent appears not to be involved. Tested individuals showed no evidence of gross chromosomal abnormality. Dominant autosomal inheritance with incomplete penetrance was indicated by the lack of expression of the defective gene in the two Angus sires and in three unaffected daughters who produced dwarf calves from matings to the Piedmontese bull. The mode of inheritance is that of a single autosomal dominant gene with a penetrance coefficient of 0.75 +/- 0.12, estimated from the observed incidence of 23/61 affected offspring of the two carrier Angus bulls mated to unrelated dams. Simple genetic models involving either (i) an unstable mutant which changes at high frequency to the expressed dominant dwarfing allele during gametogenesis, or (ii) a dominant allele with penetrance determined by an unlinked modifying locus, are shown to be compatible with the experimental data. Both models indicate that penetrance of the dwarfing gene may possibly be higher in matings involving carrier daughters of the two Angus bulls.

New genetic model rat for congenital cataracts due to a connexin 46 (Gja3 ) mutation

A rat strain with congenital nuclear cataracts has been established. Segregation analyses indicated that this phenotype had an autosomal recessive mode of inheritance, implying that a loss of function mutation of a single autosomal gene was responsible. The gene was mapped to the D15Rat6 locus on chromosome 15 through a linkage analysis using 93 backcrossed rats. The connexin 46 gene (Gja3) was found to be located close to the locus, and was regarded as a strong candidate because of its pivotal role in the lens fiber cells. Expression of the gene in the lens was comparable between the cataract and control rats when evaluated with immunohistochemistry and reverse transcription-polymerase chain reaction. However, a non-conservative missense mutation, Glu42Lys, was found in the gene of the cataract rats, which was likely to be responsible for the pathogenesis. This strain will be useful in pathophysiological studies on nuclear cataracts.

Polydactyly, Triphalangism of the Thumb, and Carpal Abnormalities in a Family

Many authors have documented the anatomic variability of radial-sided polydactyly and triphalangism of the thumb, but the relationship between these two conditions remains confusing. This study was done to determine if all types of radial-sided polydactyly and triphalangism of the thumb are related. Twenty-five members of a family with these abnormalities were evaluated clinically and radiographically by using radiographs of the hands and feet and, where appropriate, the tibia, in order to ascertain whether all variations of radial-sided polydactyly and triphalangism of the thumb could be found in this family. The hand abnormalities comprised eight types based on the number of digits, the number of phalanges, and whether the digits or phalanges were normal, hypoplastic, or rudimentary. Five distinct carpal anomalies were identified. Essentially all described types of radial-sided polydactyly and triphalangism of the thumb occur in this family. The occurrence of these abnormalities is determined by a single autosomal dominant gene. The manner in which the gene is expressed is determined either by its allele or by a combination of genetic and environmental factors. The findings in the parent cannot be used to predict the findings in the offspring.

Inherited pancreatic cancer: improvements in our understanding of genetics and screening

Inherited pancreatic cancers represent approximately 5–10% of all pancreatic cancers. Pancreatic cancer may be inherited as part of a known cancer syndrome or in association with hereditary pancreatitis or cystic fibrosis. However, most inherited pancreatic cancers do not occur in the context of a known syndrome, and these are referred to as familial pancreatic cancers. Growing evidence suggests the presence of a single autosomal dominant gene in familial pancreatic cancer kindreds, and a susceptibility locus on chromosome 4 has recently been identified in one such family. Pancreatic cancer is believed to arise from pancreatic dysplasia, and familial pancreatic cancer kindreds represent a particularly high-risk population for whom effective screening strategies are needed. One promising strategy has used endoscopic ultrasound to detected pancreatic dysplasia in members of familial pancreatic cancer kindreds.