The 2007 Census Test: evaluation of key objectives

The Office for National Statistics conducted a major census field test in May and June 2007 as part of the planning and preparation for the next census of population and housing in England and Wales in 2011. The 2007 Census Test was a large scale test covering approximately 100,000 household in five local authorities (LAs) selected to reflect a range of geographic conditions and social characteristics. Within England the Test covered parts of Bath and North East Somerset, Camden, Liverpool and Stoke on Trent. In Wales the Test took place in Carmarthenshire. The selected LAs were chosen to provide a varied cross section of the population and types of housing that would be covered in a full census. This article summarises the evaluation results and, where decided, decisions for 2011 on four key aspects of the Test: delivery method - post-out compared with hand delivery; inclusion of an income question; outsourcing recruitment, training and pay; and liaison with LAs.     

Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.     

Linkage of epidermolytic hyperkeratosis to the type II keratin gene cluster on chromosome 12q.

We investigated the molecular genetics of epidermolytic hyperkeratosis (EHK), a dominant disorder characterized by epidermal blistering, hyperkeratosis, vacuolar degeneration and clumping of keratin filaments. Based on this pathology, we have excluded by linkage analysis several candidate genes for the disease; in contrast, complete linkage was obtained with the type II keratin, K1, on 12q11-q13. Linkage in this region of chromosome 12 was confirmed using several other markers, and multi-locus linkage analyses further supported this location. Keratins are excellent EHK gene candidates since their expression is specific to the suprabasal epidermal layers. In the pedigree studied here, a type II keratin gene, very probably K1, is implicated as the site of the molecular defect causing EHK.     

The earliest evidence for anatomically modern humans in northwestern Europe

The earliest anatomically modern humans in Europe are thought to have appeared around 43,000-42,000 calendar years before present (43-42 kyr cal BP), by association with Aurignacian sites and lithic assemblages assumed to have been made by modern humans rather than by Neanderthals. However, the actual physical evidence for modern humans is extremely rare, and direct dates reach no farther back than about 41-39 kyr cal BP, leaving a gap. Here we show, using stratigraphic, chronological and archaeological data, that a fragment of human maxilla from the Kent's Cavern site, UK, dates to the earlier period. The maxilla (KC4), which was excavated in 1927, was initially diagnosed as Upper Palaeolithic modern human. In 1989, it was directly radiocarbon dated by accelerator mass spectrometry to 36.4-34.7 kyr cal BP. Using a Bayesian analysis of new ultrafiltered bone collagen dates in an ordered stratigraphic sequence at the site, we show that this date is a considerable underestimate. Instead, KC4 dates to 44.2-41.5 kyr cal BP. This makes it older than any other equivalently dated modern human specimen and directly contemporary with the latest European Neanderthals, thus making its taxonomic attribution crucial. We also show that in 13 dental traits KC4 possesses modern human rather than Neanderthal characteristics; three other traits show Neanderthal affinities and a further seven are ambiguous. KC4 therefore represents the oldest known anatomically modern human fossil in northwestern Europe, fills a key gap between the earliest dated Aurignacian remains and the earliest human skeletal remains, and demonstrates the wide and rapid dispersal of early modern humans across Europe more than 40 kyr ago.     

Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris

Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren. We have identified homozygous or compound heterozygous mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of moderate or severe ichthyosis vulgaris in 15 kindreds. In addition, these mutations are semidominant; heterozygotes show a very mild phenotype with incomplete penetrance. The mutations show a combined allele frequency of approximately 4% in populations of European ancestry, explaining the high incidence of ichthyosis vulgaris. Profilaggrin is the major protein of keratohyalin granules in the epidermis. During terminal differentiation, it is cleaved into multiple filaggrin peptides that aggregate keratin filaments. The resultant matrix is cross-linked to form a major component of the cornified cell envelope. We find that loss or reduction of this major structural protein leads to varying degrees of impaired keratinization.     

Age and growth of bluehead suckers and flannelmouth suckers in headwater tributaries, Wyoming

Bluehead sucker ( Catostomus discobolus ) and flannelmouth sucker ( Catostomus latipinnis ) populations are declining throughout these species’ native ranges in the Upper Colorado River Basin. In order to conserve these populations, an understanding of population dynamics is needed. Using age estimates from pectoral fin rays, we describe age and growth of these 2 species in 3 Wyoming stream systems: Muddy Creek, the Little Sandy River, and the Big Sandy River. Within all 3 stream systems, flannelmouth suckers were longer-lived than bluehead suckers, with maximum estimated ages of 16 years in Muddy Creek, 18 years in Little Sandy Creek, and 26 years in the Big Sandy River. Bluehead suckers had maximum estimated ages of 8 years in Muddy Creek, 10 years in Little Sandy Creek, and 18 years in the Big Sandy River. These maximum estimated ages were substantially greater than in other systems where scales have been used to estimate ages. Mean lengths at estimated ages were greater for flannelmouth suckers than for bluehead suckers in all 3 streams and generally less than values published from other systems where scales were used to estimate ages. Our observations of long life spans and slow growth rates among bluehead suckers and flannelmouth suckers were probably associated with our use of fin rays to estimate ages as well as the populations being in headwater tributaries near the northern edges of these species’ ranges.     

Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome

RAB, ADP-ribosylation factors (ARFs) and ARF-like (ARL) proteins belong to the Ras superfamily of small GTP-binding proteins and are essential for various membrane-associated intracellular trafficking processes. None of the approximately 50 known members of this family are linked to human disease. Using a bioinformatic screen for ciliary genes in combination with mutational analyses, we identified ARL6 as the gene underlying Bardet-Biedl syndrome type 3, a multisystemic disorder characterized by obesity, blindness, polydactyly, renal abnormalities and cognitive impairment. We uncovered four different homozygous substitutions in ARL6 in four unrelated families affected with Bardet-Biedl syndrome, two of which disrupt a threonine residue important for GTP binding and function of several related small GTP-binding proteins. Analysis of the Caenorhabditis elegans ARL6 homolog indicates that it is specifically expressed in ciliated cells, and that, in addition to the postulated cytoplasmic functions of ARL proteins, it undergoes intraflagellar transport. These findings implicate a small GTP-binding protein in ciliary transport and the pathogenesis of a pleiotropic disorder.     

Quality assuring the 2011 Census population estimates

The 2011 Census is a once in a decade opportunity to gain an accurate picture of the population. Quality assurance of the census population estimates is vital to ensure data robustness and that users have confidence in the results. This article provides a detailed summary of the methods being used to achieve this quality assurance, including the processes and adjustments.     

Constraints on convergence: hydrophobic hind legs allow some male pollinator fig wasps early access to submerged females

Pollinator fig wasps (Hymenoptera: Agaonidae) display numerous adaptations linked to their obligate association with fig trees (Ficus). Ceratosolen fig wasps pollinate figs that often fill temporarily with liquid, and one clade has males with unusually long hind legs. We investigated their morphology and behaviour. Scanning electron microscopy (SEM) revealed that the cuticle of their hind legs is highly modified and covered with numerous hydrophobic setae and microtrichia that can prevent blockage of the wasps’ large propodeal spiracles by liquids. In deep liquid, the males floated on the surface, but when only a thin layer of liquid was present, the legs allowed males to access females without the risk of drowning. Access to females was facilitated by an air bubble that forms between the hind legs and maintains a column of air between the spiracles and the centre of the figs. Sexual selection should favour males that can gain earlier access to mates, and the modified legs represent an adaptation to achieve this. Convergent adaptations are known in some unrelated non-pollinating fig wasps that develop in similar liquid-filled figs, but these species have enlarged hydrophobic peritremata at the ends of their metasoma to protect the spiracles located there. Unlike non-pollinating fig wasps, pollinator males need to insert their metasoma deep into females’ galls during mating. This difference in mating behaviour has constrained the extent of convergence.