Risk variables affecting high-grade Pap smears at second visit: effects of screening interval, year, age and low-grade smears.

Our aim was to study the effect, during the period 1979-1996, of the potential risk factors (i) year, age at second visit and first screening interval on the frequency of detection of low- and high-grade smears at the second visit after a normal smear at the first visit; (ii) year, age at second visit and low-grade smears at first visit on the detection of high-grade smears at second visit; (iii) detection of low- and high-grade smears by calendar year at second visit after a normal first visit (period 1981-1996); (iv) proportion of high-grade smears at second visit attributable to low-grade smears at first visit (exposed group); and (v) effect of increasing the screening interval from 2 to 5 years. The results were as follows: (i) low-grade smears increased significantly with years, high-grade smears increased significantly with screening interval and both grades decreased significantly with age; (ii) high-grade smears increased significantly with low-grade smears at first visit and with year but decreased significantly with age; (iii) a significant increase in low-grade smears at second visit with years; (iv) 97% of high-grade smears at second visit were attributable to low-grade smears at first visit; and (v) the risk of high-grade smears was 60% higher when the screening interval was 5 years rather than 2 years after a normal visit at age 20. The strongest risk factors for high-grade cell changes were low-grade smears at first visit [odds ratio 10.2 (ii) and 29.0 (iv)] and first screening interval [odds ratio 1.6 (v)].

Genetic diversity and population structure of 20 North European cattle breeds.

Blood samples were collected from 743 animals from 15 indigenous, 2 old imported, and 3 commercial North European cattle breeds. The samples were analyzed for 11 erythrocyte antigen systems, 8 proteins, and 10 microsatellites, and used to assess inter- and intrabreed genetic variation and genetic population structures. The microsatellites BoLA-DRBP1 and CSSM66 were nonneutral markers according to the Ewens-Watterson test, suggesting some kind of selection imposed on these loci. North European cattle breeds displayed generally similar levels of multilocus heterozygosity and allelic diversity. However, allelic diversity has been reduced in several breeds, which was explained by limited effective population sizes over the course of man-directed breed development and demographic bottlenecks of indigenous breeds. A tree showing genetic relationships between breeds was constructed from a matrix of random drift-based genetic distance estimates. The breeds were classified on the basis of the tree topology into four major breed groups, defined as Northern indigenous breeds, Southern breeds, Ayrshire and Friesian breeds, and Jersey. Grouping of Nordic breeds was supported by documented breed history and geographical divisions of native breeding regions of indigenous cattle. Divergence estimates between Icelandic cattle and indigenous breeds suggested a separation time of more than 1,000 years between Icelandic cattle and Norwegian native breeds, a finding consistent with historical evidence.

Frequencies of genes for coat colour and horns in Nordic cattle breeds.

Gene frequencies of coat colour and horn types were assessed in 22 Nordic cattle breeds in a project aimed at establishing genetic profiles of the breeds under study. The coat colour loci yielding information on genetic variation were: extension, agouti, spotting, brindle, dun dilution and colour sided. The polled locus was assessed for two alleles. A profound variation between breeds was observed in the frequencies of both colour and horn alleles, with the older breeds generally showing greater variation in observed colour, horn types and segregating alleles than the modern breeds. The correspondence between the present genetic distance matrix and previous molecular marker distance matrices was low (r = 0.08 - 0.12). The branching pattern of a neighbour-joining tree disagreed to some extent with the molecular data structure. The current data indicates that 70% of the total genetic variation could be explained by differences between the breeds, suggesting a much greater breed differentiation than typically found at protein and microsatellite loci. The marked differentiation of the cattle breeds and observed disagreements with the results from the previous molecular data in the topology of the phylogenetic trees are most likely a result of selection on phenotypic characters analysed in this study.

Comparison of milk protein allele frequencies in Nordic cattle breeds.

Allele frequencies at four milk protein loci were studied in five modern and 17 old Nordic cattle breeds in order to reveal variants that are characteristic for these populations. The B allele of CSN3, which has been associated with improved manufacturing properties of milk, showed significantly lower frequencies in modern production breeds than in old breeds of interest for conservation purposes. Characteristic frequencies of CSN1S1 (C), CSN2 (A2) and CSN3 (B) were found in Icelandic cattle, Swedish Mountain cattle, Northern Finncattle and Western Fjord cattle, which indicate a common origin of these populations. Further comparisons of allele frequencies in old Nordic breeds suggest sorting of these breeds into two groups with a northern and southern geographic location.

Temporal changes in genetic variation of north European cattle breeds.

Temporal changes in genetic variation within and between 13 North European cattle breeds were evaluated using erythrocyte antigen systems and transferrin protein as genetic markers. Current data on allele frequency distributions of markers in large commercial and smaller endangered native cattle breeds were compared to data published during 1956 to 1975. Intrabreed genetic variation was quantified by conventional parameters (e.g. heterozygosity, average number of alleles per locus) and migration by the effective migration rate. The neighbour-joining dendrogram of relationships between old and present cattle populations was constructed using Nei's standard genetic distance. Variance effective population size was estimated from changes in allele frequencies over time. Comparison of old and new data indicated some significant changes in allele frequencies. In six of the breeds, a few low-frequency alleles in the old data were absent in the present samples. Heterozygosity remained stable in most breeds. The harmonic means for variance effective population size ranged between 30 and 257. Current results indicate that despite marked declines in total population sizes, North European native cattle breeds have retained a reasonably high genetic diversity. However, their genes contribute less than previously to genetic variation of Nordic production breeds. Commercial breeds do not appear to have a larger effective population size than native breeds. The present effective population sizes imply that Nordic breeds could have lost from 1 to 11% of their heterozygosity over a 20-40-year period.

A non-epistatic interaction of agouti and extension in the fox, Vulpes vulpes.

Agouti and extension are two genes that control the production of yellow-red (phaeomelanin) and brown-black (eumelanin) pigments in the mammalian coat. Extension encodes the melanocyte-stimulating hormone receptor (MC1R) while agouti encodes a peptide antagonist of the receptor. In the mouse, extension is epistatic to agouti, hence dominant mutants of the MC1R encoding constitutively active receptors are not inhibited by the agouti antagonist, and animals with dominant alleles of both loci remain darkly pigmented. In the fox the proposed extension locus is not epistatic to the agouti locus. We have cloned and characterized the MC1R and the agouti gene in coat colour variants of the fox (Vulpes vulpes). A constitutively activating C125R mutation in the MC1R was found specifically in darkly pigmented animals carrying the Alaska Silver allele (EA). A deletion in the first coding exon of the agouti gene was found associated with the proposed recessive allele of agouti in the darkly pigmented Standard Silver fox (aa). Thus, as in the mouse, dark pigmentation can be caused by a constitutively active MC1R, or homozygous recessive status at the agouti locus. Our results, demonstrating the presence of dominant extension alleles in foxes with significant red coat colouration, suggest the ability of the fox agouti protein to counteract the signalling activity of a constitutively active fox MC1R.

The role of melanocyte-stimulating hormone (MSH) receptor in bovine coat color determination.

The melanocyte-stimulating hormone (MSH) receptor has a major function in the regulation of black (eumelanin) versus red (phaeomelanin) pigment synthesis within melanocytes. We report three alleles of the MSH-receptor gene found in cattle. A point mutation in the dominant allele ED gives black coat color, whereas a frameshift mutation, producing a prematurely terminated receptor, in homozygous e/e animals, produces red coat color. The wild-type allele E+ produces a variety of colors, reflecting the possibilities for regulating the normal receptor. Microsatellite analysis, RFLP studies, and coat color information were used to localize the MSH-receptor to bovine Chromosome (Chr) 18.

Brown coat color in Icelandic cattle produced by the loci Extension and Agouti.

Inheritance of the colors black, brown, and red in Icelandic cattle was studied. The three colors are produced by two loci, Extension (E) and Agouti (A), with three alleles at the E locus: E(d) for dominant black; E+, intermediate, which allows expression of A locus alleles; and e for recessive red color. Two alleles are postulated at the A locus: A+, producing brown, and a, producing recessive black (nonagouti) when homozygous in E+/- animals. The dominant and recessive types of black are indistinguishable from each other phenotypically. The A alleles are only able to express their effect in E+/- genotypes. The E and A loci in cattle are postulated to be homologous to the E and A loci in the mouse.

Inheritance of goat coat colors.

Goat color inheritance was evaluated based on color description of 218 kids and their parents (10 sires, 178 dams) from mixed crosses between several goat populations in an experiment on cashmere fiber production. Altogether 10 color patterns were observed. They were postulated to be caused by 10 alleles at the Agouti locus, with the allele for white or tan color being the top dominant allele, and the nine others codominant. The bottom recessive allele, for nonagouti color, was the 11th allele at this locus. The postulated alleles are white or tan (A(wt)), black mask (A(blm)), bezoar (A(bz)), badgerface (A(b)), grey (A(g)), lightbelly (A(lb)), swiss markings (A(sm)), lateral stripes (A(ls)), mahogany (A(mh)), red cheek (A(rc)), and nonagouti (Aa). Two types of eumelanin pigment were observed, black and light brown, the latter being dominant. Recessive brown was not observed.

Reciprocal translocation (13;20)(q12;q22) in an Icelandic sheep.

Cytogenetic examination of G-banded lymphocyte chromosomes of an Icelandic ram from a line with a history of poor fertility revealed a rcp (13;20) (q12;q22) translocation. Meiotic studies showed a quadrivalent configuration at diakinesis and this was confirmed by C-banding.

Trends in cervical and breast cancer in Iceland. A statistical evaluation of trends in incidence and mortality for the period 1955-1989, their relation to screening and prediction to the year 2000.

The time trends in incidence and mortality from cervical cancer and breast cancer in Iceland, from 1955 to 1989, were analyzed by fitting curvilinear regressions to the age-standardized rates. The effect of the screening was evaluated by comparing the curvature of the fitted regression lines and changes in screening activity. The incidence and mortality rates for both cancer types were predicted up to the year 2000. At the commencement of cervical cancer screening in 1964, both the incidence and mortality rates were on the increase. After 1970, both rates decreased significantly. Assuming that regular attendance at screening will be 85%, it is predicted that the incidence and mortality rates will level out at about 7.5 and 2 cases per 100,000 women per year, respectively, by the year 1995 and remain at that level. The incidence of breast cancer has increased steadily since 1955. A sharp rise has been observed since 1987, due to screening with mammography. The mortality rate has shown small but significant fluctuations with time. The incidence rate is predicted to increase at the same rate as before 1987 (i.e. at 1.1 cases per 100,000 women per year), but at a slightly higher level and is predicted to reach 84 cases per 100,000 women per year by the year 2000. Breast cancer mortality is predicted to decrease to about 17 cases per 100,000 women per year by 1995 and to remain at that level.

Prevalence and geographical distribution of the ear canker mite (Otodectes cynotis) among arctic foxes (Alopex lagopus) in Iceland.

Three hundred forty five adult arctic foxes (Alopex lagopus) from all counties in Iceland were examined for excess cerumen and ear canker mites (Otodectes cynotis). Only 13 foxes (4%) from a single county in northwestern Iceland were infested, where the prevalence of otodectiasis was 38%. Whether or not this parasite is new to the arctic fox in Iceland is unknown. If it is recently introduced, possible sources of infestation are farmed silver foxes (Vulpes vulpes), domestic dogs, domestic or feral cats, and arctic foxes from Greenland. It appears that the rate of transmission between adult foxes is low; a more common route of transmission is probably from the mother to her offspring or between vixens breeding in the same dens in subsequent years by contamination of the dens. No correlation was found between the prevalence of mites in foxes and Samson character.

The value of screening as an approach to cervical cancer control in Iceland, 1964-1986.

The effect of screening for cervical cancer on time trends in incidence and mortality from that disease, and the occurrence of pre-invasive cervical lesions during the period 1964-1986, were analyzed. After commencement of screening in 1964 all the above parameters increased for a short initial period but then fell markedly. From 1980, coinciding with a sharp rise in regular attendance rate, there was an increase in incidence up to 1984, followed by a decrease. The rate of pre-invasive stages also increased from 1980, but appears to be levelling off. The cervical cancer mortality rate decreased significantly during the study period. In more recent years, a shift in the occurrence of cervical cancer and pre-invasive lesions from older to younger women has been observed. Screening still appears to be effective in the control of squamous-cell carcinomas of stages I B and over, but not of adeno- and adenosquamous carcinomas.

Fox colors in relation to colors in mice and sheep.

Color inheritance in foxes is explained in terms of homology between color loci in foxes, mice, and sheep. The hypothesis presented suggests that the loci A (agouti), B (black/chocolate brown pigment) and E (extension of eumelanin vs. phaeomelanin) all occur in foxes, both the red fox, Vulpes vulpes, and the arctic fox, Alopex lagopus. Two alleles are postulated at each locus in each species. At the A locus, the (top) dominant allele in the red fox, Ar, produces red color and the corresponding allele in the arctic fox, Aw, produces the winter-white color. The bottom recessive allele in both species is a, which results in the black color of the silver fox and a rare black color in the Icelandic arctic fox when homozygous. The B alleles are assumed to be similar in both species: B, dominant, producing black eumelanin, and b, recessive, producing chocolate brown eumelanin when homozygous. The recessive E allele at the E locus in homozygous form has no effect on the phenotype determined by alleles at the A locus, while Ed, the dominant allele is epistatic to the A alleles and results in Alaska black in the red fox and the dark phase in the arctic fox. Genetic formulae of various color forms of red and arctic fox and their hybrids are presented.

Electron spin resonance spectrometrical study of the melanins in the wool of some North European sheep in relation to their color inheritance.

Additional peaks that were known on the esr-spectrograms of red human and reddish-brown Karakul hair to be diagnostic traits of phaeomelanin esr-signal also were found on esr-spectrograms of the tan, but not of black or chocolate brown wool from Icelandic sheep. This tan color is thought to depend on the presence of phaeomelanin and is due to the top dominant allele at the A locus. The two methods of distinguishing between eu- and phaeomelanin-dependent brown colors--esr-spectrometrical and genetical--are in agreement for European as well as for Asiatic breeds. Both light and dark brown Soay fleece samples lacked the additional peaks and are interpreted as eumelanin pigmentation.

Possible changes in the frequency of the human ABO blood groups in Iceland due to smallpox epidemics selection.

The hypothesis is put forward that the low frequency of A and high frequency of O blood group genes in the Icelandic human population is the result of a selective disadvantage of A during severe smallpox epidemics. The hypothesis is supported by data from India in 1965-6, which show a marked selective effect of a smallpox epidemic against the phenotypes A and AB (Vogel & Chakravartti, 1971). The conclusion is drawn that the present-day ABO blood group gene frequencies of the Icelandic population should be used with reservation as markers in the study of the origin of the Icelanders.

Inheritance of spina bifida in Icelandic lambs.

A congenital neural tube defect, spina bifida, detected in Icelandic sheep was examined and compared with similar defects reported in humans and other animals. Pedigree analysis of 29 affected lambs in two neighboring flocks showed that 27 of these cases from the sire's side and 25 from the dam's side, can be traced back to a ram (no. 1) that was one of the foundation sires of the flock at Skriduklaustur where most of the affected lambs were born. Among the exceptions, two on the sire's side and one on the dam's side can be traced back to ewe no. 323 used at Skriduklaustur; another three affected animals can be traced through the dam's side to ewe no. 35 also used at Skriduklaustur, and to ewes E1 and E301 used at Eyrarland farm. All of the four ewes appear to be related to ram no. 1, although information on their parentage is not available from the flock record. The occurrence and frequency of this condition in the two flocks indicate that spina bifida is transmitted as an autosomal recessive trait in Icelandic sheep.

A black-moorit mosaic-colored Icelandic ram.

A description is given of a black-moorit (black-chocolate brown) mosaic male lamb born in Iceland in the spring of 1982. A testmating resulted in 10 moorit and no black offspring from moorit dams. The results suggest that the mosaic color resulted from a mutation of the recessive allele b for moorit pigment to the dominant allele B for black pigment during fetal development, and that the mutation has not affected the gonadal tissue.

Two-dimensional electrophoresis of horse serum proteins: genetic polymorphism of ceruloplasmin and two other serum proteins.

Two-dimensional agarose gel (pH 8.6)-horizontal polyacrylamide gel (pH 9.0) electrophoresis of horse serum proteins revealed genetic polymorphism of ceruloplasmin (Cp) and two unidentified serum proteins tentatively designated serum protein 1 (SP1) and serum protein 2 (SP2). Family data were consistent with the hypothesis that the observed Cp and SP1 phenotypes were each controlled by two codominant, autosomal alleles. The three common SP2 phenotypes were shown to be controlled by two codominant, autosomal alleles. Population data and limited family data indicated the occurrence of two additional SP2 alleles. Altogether more than 600 horses representing 13 different breeds were typed for Cp, SP1 and SP2, and allele frequency estimates were calculated. SP2 was highly polymorphic in all breeds studied whereas SP1 and Cp showed quite low degrees of polymorphism. SP1 polymorphism was observed in seven breeds while Cp polymorphism was observed only in the Icelandic toelter horse breed.

Linkage of the equine serum esterase (Es) and mitochondrial glutamate oxaloacetate transaminase (GOTM) loci. A horse-mouse homology.

Three previously described electrophoretic phenotypes of mitochondrial glutamate oxaloacetate transaminase (GOTM) in horse leukocytes are shown to be controlled by two codominant alleles at a single autosomal locus. The GOTM locus is linked to the serum esterase locus (Es), as no recombination between these loci was observed among 16 informative offspring in one sire family. The results assign GOTM to equine linkage group (LG) II. The hypothesis that a part of LG II (e-Es) shares homologies with mouse chromosome 8 is thus confirmed, as the murine homologue of GOTM is located within the cluster of esterase loci on chromosome 8. The assumed homology also involves rabbit LG VI, rat LG V, and human chromosome 16. The observation is a striking example of the conservation of linkage relationships between mammalian species.