Detection of putative loci affecting conformational type traits in an elite population of United States Holsteins using microsatellite markers

Quantitative trait loci affecting conformational type traits were studied in seven large grandsire families of US Holsteins using the granddaughter design and 16 microsatellite markers on 10 chromosomes. The most significant marker effect was marker BM203 (chromosome 27) for dairy form in a single grandsire family. A multivariate analysis for dairy form and milk yield was also conducted, and the result was highly significant, indicating that a segregating quantitative trait locus or loci affecting dairy form and milk yield could exist near BM203 on chromosome 27. Marker BM1258 (chromosome 23) had a significant effect on udder depth. A multivariate analysis on udder depth and somatic cell score was conducted for markers 513 and BM1258, and both markers showed significant effects on these two traits, indicating that one or several quantitative trait loci affecting udder depth and mastitis might exist on chromosome 23. Marker BM4204 (chromosome 9) had a significant effect on foot angle and on the composite index of traits pertaining to feet and legs, indicating that one or several quantitative trait loci affecting traits pertaining to feet and legs might exist on chromosome 9. Selection on these markers could increase genetic progress within these families.     

Variances of direct genetic effects, maternal genetic effects, and cytoplasmic inheritance effects for milk yield, fat yield, and fat percentage

Milk yield, fat yield, and fat percentage during the first three lactations were studied using New York Holsteins that were milked twice daily over a 305-d, mature equivalent lactation. Those data were used to estimate variances from direct and maternal genetic effects, cytoplasmic effects, sire by herd interaction, and cow permanent environmental effects. Cytoplasmic line was traced to the last female ancestor using DHI records from 1950 through 1991. Records were 138,869 lactations of 68,063 cows calving from 1980 through 1991. Ten random samples were based on herd code. Samples averaged 4926 dams and 2026 cytoplasmic lines. Model also included herd-year-seasons as fixed effects and genetic covariance for direct-maternal effects. Mean estimates of the effects of maternal genetic variances and direct-maternal covariances, as fractions of phenotypic variances, were 0.008 and 0.007 for milk yield, 0.010 and 0.010 for fat yield, and 0.006 and 0.025 for fat percentage, respectively. Average fractions of variance from cytoplasmic line were 0.011, 0.008, and 0.009 for milk yield, fat yield, and fat percentage. Removal of maternal genetic effects and covariance for maternal direct effects from the model increased the fraction of direct genetic variance by 0.014, 0.021, and 0.046 for milk yield, fat yield, and fat percentage; little change in the fraction was due to cytoplasmic line. Exclusion of cytoplasmic effects from the model increased the ratio of additive direct genetic variance to phenotypic variance by less than 2%. Similarly, when sire by herd interaction was excluded, the ratio of direct genetic variance to phenotypic variance increased 1% or less.     

Event-time analysis of reproductive traits of dairy heifers

Data on the reproductive traits of dairy heifers were analyzed using event-time techniques. Traits analyzed were age at first calving (n = 4631), days to first breeding, and days open (n = 1992) during the first lactation. A proportional hazard model was used that included fixed effects of herd-year, year-season, breed type, herd weight, and heifer weight. Body weights were recorded at 390 d of age, on average. The model for days open and days to first breeding included two additional fixed effects of herd and heifer milk yield at 100 d. A significant effect of heifer weight category on age at first calving was found. The chance of calving was consistently higher for herds and heifers with higher body weight at 390 d and decreased linearly from the top to the lowest quartiles. The effects of herd weight category on days to first breeding and days open were significant. Heifers in herds with a higher average body weight were less likely to be bred, and heifers in herds with lower average body weight were less likely to get pregnant. The effect of heifer weight category on days to first breeding or days open was not significant. The effect of herd milk yield on days to first breeding was significant. Heifers in herds with lower yield were more likely to be bred. The effect of heifer milk yield category on days to first breeding and days open was significant, but no linear trend was found for the estimates of the hazard ratios. The chance of a heifer being bred and becoming pregnant was similar among the first three quartiles and was lower for heifers in the lowest quartile. The probability of a heifer reaching a first calving can be improved by increasing the body weight at 390 d. Body weight at 390 d did not appear to have a large effect on reproductive performance after first calving. High milk yield appears not to have a large negative effect on days open, at least for the milk yield levels analyzed in this study.     

Use of linear type and production data to supplement early predicted transmitting abilities for productive life

Genetic evaluations for the length of productive life based on actual DHIA culling data have been available in the US since January 1994. Although substantial genetic variation in productive life exists, the reliability of selection is often low, particularly for recently progeny-tested bulls having daughters that have not yet had an opportunity to be culled. Correlated production and conformation traits, which have higher heritability than productive life and are available earlier in life, may be used to enhance evaluations of productive life for young bulls that have little or no direct culling information available. Genetic correlations between productive life and milk, fat, dairy form, and udder traits ranged from +0.22 to +0.46. The maximum reliability of the indirect prediction of productive life from 16 correlated type and production traits was 0.56, and the maximum reliability from a subset of 10 traits was 0.51. Indirect information about productive life that was derived from type and production traits was combined with actual culling information to increase the total amount of available information for many recently progeny-tested bulls. The procedures described herein for enhancing direct evaluations for the productive life of dairy sires with indirect information about production and type were implemented by the USDA Animal Improvement Programs Laboratory and the Holstein Association USA in July 1994.     

Covariance functions across herd production levels for test day records on milk, fat, and protein yields

Multiple-trait BLUP evaluations of test day records require a large number of genetic parameters. This study estimated covariances with a reduced model that included covariance functions in two dimensions (stage of lactation and herd production level) and all three yield traits. Records came from all six states in Australia, were evenly distributed across the herd production levels, but decreased with increasing lactation stage from 9693 records for the 1st mo of lactation to 4199 records for the 10th mo. Using the variance component estimation package and a bivariate animal model, 1176 genetic (co)variances and 312 environmental (co)variances were estimated for 48 traits (1, 4, 7, and 10 mo of lactation; herd production levels of < 20, 20 to 22, 22 to 24, > 24 kg of milk/d; and milk, fat, and protein yields). The genetic (co)variances could be predicted by a multiplicative model that included 1) a term dependent on which yields (milk, fat, or protein) were involved in the covariance, 2) the covariance functions for month of lactation and herd production level, and 3) a covariance function for the interaction between these. This model required only 27 parameters instead of the 1176 (co)variances. For the environmental (co)variances, a model was fitted that contained several additional covariance functions. This model reduced the number of parameters from 312 to 71. For the same trait at the same production level, genetic correlations between test days ranged from 0.59 to 1, and environmental correlations ranged from 0.17 to 0.48. Genetic correlations between milk and fat, milk and protein, and fat and protein were 0.38, 0.83, 0.59, respectively, and correlations between the herd production levels ranged from 0.79 to 0.97. Failure to consider herd production level in a test day model evaluation might result, for instance, in overweighting of early lactation information from high production herds compared with information coming from bulls tested across all production levels.     

Blood groups and milk and type traits in dairy cattle: after forty years of research

This study addresses the utility of 11 blood groups as selection aids in Holstein breeding schemes and considers issues inherent to the approach of resolving quantitative variation into components that are due to quantitative trait loci. The data consisted of predicted transmitting abilities of 22,614 bulls, first lactation information on 1,924,171 cows, and type scores on 447,800 cows. Linear models were fitted under male half-sib designs, female half-sib designs, and granddaughter designs as well as under the assumption of direct effects of the markers. The evolution of allele frequencies through time was determined, and previous research results were synthesized according to criteria of consistency of biological significance. The inconsistency of results across studies and analytical designs alludes to the importance of the intrinsic nonadditivity of genetic and biological phenomena to quantitative trait locus detection and marker-assisted selection. In our analyses, three associations met the criteria of consistency--a C blood group effect on rump angle, an L effect on milk yield and composition traits, and an S effect on milk fat yield. The M locus appears to be directly associated with effects on milk and protein yields. An enhanced understanding of the biochemical and physiological bases of quantitative genetics should be a long-term objective of this type of genetic analysis.     

Mapping quantitative trait loci for carcass and meat quality traits in a wild boar x Large White intercross

An intercross between wild boar and a domestic Large White pig population was used to map quantitative trait loci (QTL) for body proportions, weight of internal organs, carcass composition, and meat quality. The results concerning growth traits and fat deposition traits have been reported elsewhere. In the present study, all 200 F2 animals, their parents, and their grandparents were genotyped for 236 markers. The marker genotypes were used to calculate the additive and dominance coefficients at fixed positions in the genome of each F2 animal, and the trait values were regressed onto these coefficients in intervals of 1 cM. In addition, the effect of proportion of wild boar alleles was tested for each chromosome. Significant QTL effects were found for percentage lean meat and percentage lean meat plus bone in various cuts, proportion of bone in relation to lean meat in ham, muscle area, and carcass length. The significant QTL were located on chromosomes 2, 3, 4, and 8. Each QTL explained 9 to 16% of the residual variance of the traits. Gene action for most QTL was largely additive. For meat quality traits, there were no QTL that reached the significance threshold. However, the average proportion of wild boar alleles across the genome had highly significant effects on reflectance and drip loss. The results show that there are several chromosome regions with a considerable effect on carcass traits in pigs.     

Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23

Transient neonatal diabetes mellitus (TNDM) is a rare form of childhood diabetes which usually resolves in the first 6 months of life but which predisposes to type 2 diabetes of adult onset. We recently reported paternal uniparental isodisomy of chromosome 6 (UPD6) in two children with TNDM and proposed that there may be an imprinted gene important in the aetiology of diabetes on chromosome 6. We now describe two unrelated families which independently suggest that the gene is imprinted, is paternally expressed and maps to 6q22-q23. One family has a duplication while the other, with familial TNDM, shows linkage to a marker in this region.     

Genetic heterogeneity of autosomal dominant cerebellar ataxia type 1: clinical and genetic analysis of 10 French families

We performed linkage analysis between the gene responsible for spinal cerebellar ataxia 1 (SCA1) and the highly polymorphic chromosome 6 locus, D6S89, in 10 French families with autosomal dominant cerebellar ataxia (ADCA) type 1. These families were clinically indistinguishable except for one family with loss of hearing and vision. Very close linkage was observed in four families, with no evidence of recombination between SCA1 and D6S89. Linkage with D6S89 was excluded in the six others, thus demonstrating genetic heterogeneity for ADCA type 1. The D6S89 marker, which is very closely linked to the disease locus, can be used to identify SCA1 families and will lead to predictive testing.     

Effects of level and type of energy source (volatile fatty acids or glucose) on milk yield, composition and coagulating properties in dairy cows

Four fistulated Holstein cows were arranged in a 4 x 4 Latin square design to study the effects of level and type of energy source on milk yield and composition. Treatments consisted of a basal diet fed alone (low energy treatment) or with 3.3 Mcal of net energy for lactation from extra nutrients perfused either into the rumen (either propionic acid or a mixture of volatile fatty acids) or into the duodenum (glucose). Increasing the energy input without changing the volatile fatty acid profile improved milk yield and slightly increased milk protein and fat yields. Compared with the isoenergetic mixture of volatile fatty acids, both propionic acid and glucose infusions significantly decreased fat content (-4.5 g/kg) and yields (respectively, -111 and -160 g/d), but affected fatty acid proportion and yield differently (more elongation process and less C18 with glucose infusion). Protein yield was slightly increased by propionic acid infusion but not by glucose because of the counterbalanced effects on milk yield (-1.3 kg/d) and protein content (1.5 g/kg). The coagulating properties of milk were directly linked to variations in protein, casein and mineral contents. In conclusion, propionic acid or glucose scarcely affected milk protein content, but induced a similar decrease in milk fat content probably through different metabolic pathways.     

The effects of inbreeding on the lifetime performance of dairy cattle

The effects of inbreeding on the lifetime performance of dairy cattle were examined using data for production, somatic cell score, and linear type for all Holstein cows that were scored between 1983 and 1993. The results of fixed and mixed animal models differed. Relative net income adjusted for opportunity cost for the 2,610,123 cows with an 84-mo opportunity for herdlife was depressed by $14.79 for fluid market pricing and by $12.40 for manufacturing pricing per 1% increase in inbreeding. Mixed model estimates of depression per 1% of increase in inbreeding were +0.55 d for age at first calving, -6 d for days of productive life, and -4.8 for days in milk. Inbreeding decreased the mature equivalent production of milk, fat, and protein during first lactation by 27, 0.9, and 0.8 kg and the lifetime production of milk, fat, and protein by 177, 6.0, and 5.5 kg, respectively, per 1% increase in inbreeding. Inbreeding had little effect on conformation traits. The effects of inbreeding were cumulative, and effects on lifetime profit functions were relatively larger than the effects on lactation traits. Registered cows had higher levels of inbreeding and larger standard deviations than did grade cows. Inbreeding in registered cows depressed relative net income adjusted for opportunity cost for fluid and manufacturing prices by $24.43 and $21.78, respectively; income was depressed $9.43 and $9.02, respectively, for grade cows. The difference between registered and grade cattle is likely due to the incomplete pedigree information in grade animals. Inbreeding among cows in this study was not high on average, but economic losses represented a significant cost to the producer.     

Effect of added dietary fat on performance, rumen characteristics, and plasma metabolites of midlactation dairy cows

Effects of supplemental Jet-Sploded canola seed in the diets of dairy cows on milk yield and composition and blood metabolite concentrations were investigated. Twenty multiparous and 5 primiparous midlactation Holstein cows were assigned to treatments following a 3-wk covariate period; cows were then on the treatments for 70 d. Ten of the cows had previously been fitted with rumen cannulas. Five concentrate mixtures containing 0, 7.5, 15, 22, or 29% Jet-Sploded canola seed (Simons Feed Co., Quimby, IA) (equivalent to 0, 2.66, 5.33, 7.81, and 10.30% added fat, respectively) were formulated by substituting Jet-Sploded canola seed for barley and canola meal. Diets consisted of 25% alfalfa silage, 25% whole-crop oat silage, and 50% of one of the concentrate mixtures (dry matter basis). An increase in the amount of dietary fat from Jet-Sploded canola seed did not influence feed intake, milk yield or composition, or milk component yields. The inclusion of Jet-Sploded canola seed in the diet increased long-chain fatty acids and inhibited de novo synthesis of medium-chain fatty acids in milk. Mean total volatile fatty acids in the rumen and propionate concentration were reduced in a linear fashion by treatment. The inclusion of Jet-Sploded canola seed in the diets of mid-lactation cows altered rumen and blood metabolite concentrations; however, these changes had minimal effects on yield responses with the exception of milk fatty acid composition and milk protein content.     

Frequencies and effects of alternative DRB3.2 alleles of bovine lymphocyte antigen for Holsteins in milk selection and control lines

Frequencies of alleles at the DRB3.2 locus of the bovine major histocompatibility complex for two genetic lines of Holsteins were compared, and allelic effects on yield and udder health traits were examined. The DRB3.2 genotypes of 186 cows and heifers were determined using DNA that had been extracted from blood samples. The cattle were from a designed selection experiment for milk yield. After edits, 173 cows and heifers with known alleles remained (54 from a control line and 119 from a selection line for milk yield). A total of 19 alternative DRB3.2 alleles appeared across the two lines, and frequencies ranged from 0.3 to 21.4%. Allelic frequencies differed significantly between the selection and control lines. Alleles 3, 8, 9, 10, 26, and 28 were more frequent in the control line, but alleles 16, 24, and 27 were more frequent in the selection line. An animal model was used to estimate gene substitution effects of alternative alleles on milk yield, fat yield, and protein yield, SCS, chronically elevated SCS, acutely elevated SCS, and mastitis incidence. First, second, and third lactations were analyzed separately. Allele 7 was associated with a significant increase in protein yield during first and second lactations and a significant increase in chronically elevated SCS and acutely elevated SCS during second lactation. Because of conflicting results with other studies and a limited numbers of cows, additional research is needed before specific alleles are confirmed to be associated with measures of yield and udder health.     

Production and reproductive responses to use of DairyMAN: a management information system for New Zealand dairy herds

To assess the benefits of on-farm use of a computerized management information system (DairyMAN, Department of Veterinary Clinical Science, Massey University, Palmerston North, New Zealand) on seasonally calving herds of New Zealand, data for 144 herds using this system were compared with a stratified random sample of 294 herds using only the centralized National Dairy Database system during the season 1993 to 1994. Demographic, reproductive performance, and milk yield indices were compared. Herds using DairyMAN had superior reproductive outcomes, measured as a higher percentage (+8.4%) of cows calving during the desired seasonal period (critical in this seasonal system) and a higher percentage of cows (+9.7%) mated at the optimal time to achieve a concentrated calving in the following year. Multiple analysis of covariance was used to differentiate effects. The superior performance was not associated with differences in some of the more commonly used reproductive indices (efficiency of estrus detection, first service nonreturn rate, and pregnancy rate), but the data used in the study do not accurately reflect true performance. Herds using DairyMAN had more information on breeding performance because pregnancy data were available and natural breedings were recorded for a longer period. With cows of equivalent genetic merit, herds using DairyMAN produced more milk (+1.2 L/d per cow) indicating that users achieved better management of the herd through improved attention to managerial details. This improved production was associated with the adoption of DairyMAN but is not shown by this study to be a direct consequence of it. DairyMAN user herds were larger (245 cows) than were herds not using the system (181 cows), but this difference did not significantly affect the various outcomes measured.     

Genetic evaluation for herd life in Canada

Methods were developed for the national genetic evaluation of herd life for Canadian Holstein sires. The genetic evaluations incorporate information from survival (direct herd life) and information from conformation traits that are related to herd life (indirect herd life) after adjustment for production in first lactation to remove the effect of culling for production. Direct genetic evaluations for herd life were based on survival in each of the first three lactations, which was analyzed using a multiple-trait animal model. Sire evaluations thus obtained for survival in each of the first three lactations were combined based on their economic weights into an overall sire evaluation for direct herd life. Sire evaluations for indirect herd life were based on an index of sire evaluations for mammary system, feet and legs, rump, and capacity. A multiple-trait sire model based on multiple-trait across country evaluation methodology was used to combine direct and indirect genetic evaluations for herd life into an overall genetic evaluation for herd life. Sire evaluations for herd life were expressed in estimated transmitting ability as the number of lactations and represent expected differences among daughters in functional herd life (number of lactations); the average functional herd life was set equal to three lactations. Estimated transmitting abilities were normally distributed and ranged from 2.31 to 3.43 lactations.     

Chromosome 17 and hereditary dementia: linkage studies in three non-Alzheimer families and kindreds with late-onset FAD

Several previous families with differing clinical and pathologic characteristics have demonstrated linkage to the 17q21-22 region. We have performed a linkage analysis with chromosome 17 markers on three families showing autosomal dominant inheritance of non-Alzheimer dementia and 60 kindreds with late-onset familial Alzheimer's disease (FAD). Family A shows unequivocal evidence of linkage with a maximum lod score of 5.0 for marker D17S934 (theta = 0.001). This family has an unusual syndrome of a schizophrenia-like psychosis beginning in the fifth or sixth decade followed by severe dementia with an average disease duration of 13.8 years. Neuropathology from five autopsies in this family has shown marked neurofibrillary tangle formation (NFT), degeneration of the amygdala, and no amyloid plaques. This confirms the presence of a gene associated with dementia on 17q and extends the related phenotype to include schizophrenia-like symptoms and classic NFT pathology. A second family with early aphasia progressing to dementia and cortical-basal ganglion-like degeneration also has suggestive evidence for linkage to 17q. A third family with very early-onset dementia (mean, 31 years) and nonspecific pathology can be excluded from the 17q region and emphasizes additional genetic heterogeneity in non-Alzheimer hereditary dementia. Finally, we also present evidence against linkage to D17S579 in the set of 60 families with late-onset FAD, providing further evidence that the chromosome 17 gene is unlikely to be involved in the pathogenesis of typical AD.     

Biochemical and technological characteristics of the milk from Black-and White Dutch]

Studied were the composition and the technologic properties of the milk of Dutch Black pied cattle under this country's conditions. Milk samples were taken for analysis once in a month on a cow farm founded in 1964 with a total of 67 impregnated heifers and having at the time of investigation 88 cows, twelve of them remaining from the initial animals imported from Holland and the others being the offspring of the herd. It was established that the annual milk yield per forage cow, amounting to 44881 has the following index values; dry matter--12.63 +/- 0.48 per cent; butterfat per cent--4.07 +/- 0.2%; total protein--3.37 +/- 0.16 per cent; casein--2.56 +/- 0.16; slids-nonfat--8.54 +/- 0.24 per cent; calcium--0.126 +/- 0.002 per cent; phosphorus--0.079 +/- 0.003 per cent. The technologic properties of milk proved unsatisfactory: coagulation capacity--359 s; rheologic value--112.93 X 1.10(-5) V/cm3; and technologic coeficient--1.32. The data on the composition and the technologic properties of Dutch Black-pied cow's milk showed, on the whole, that most profitable is its processing into butter as against processing into cheese in which case the yields would be unsatisfactory.     

Variations with breed, age, season, yield, stage of lactation and herd in the concentration of urea in bulk milk and individual cow's milk

The concentration of urea in the milk of 510 dairy cows in 10 herds was determined at regular intervals for a year. The herds contained approximately equal numbers of Swedish Red and White, and Swedish Holstein cows. The mean +/- sd concentration in the samples from individual cows was 5.32 +/- 1.13 mmol/l, and the mean concentration in bulk milk was 5.39 +/- 0.96 mmol/l. These values indicated that on average the herds were fed too much protein relative to their intake of energy throughout the year. Herd factors had a strong influence on the milk urea concentration. The concentration was lower during the first month of lactation than later in the lactation, and lower when the cows were housed during the winter than when they were grazing. There was a weak positive relationship between the daily milk yield and urea concentration, particularly during late lactation, but there was no relationship with either breed or age. Bulk milk urea was a reliable guide to the average urea concentration of a herd.     

Evaluation of the ovine callipyge locus: II. Genotypic effects on growth, slaughter, and carcass traits

A resource flock of 362 F2 lambs provided phenotypic and genotypic data to estimate effects of callipyge (CLPG) genotypes on growth, slaughter, and carcass traits. Lambs were serially slaughtered in six groups at 3-wk intervals starting at 23 wk of age to allow comparisons at different end points. Probabilities of CLPG genotypes were calculated at a position 86 cM from the most centromeric marker of chromosome 18. A contrast of CLPG genotypic effects, based on the paternal polar overdominance model, was used to evaluate callipyge and normal phenotypes. Relationships of traits with slaughter age, carcass weight, or 12th-rib fat depth for callipyge and normal phenotypic groups were estimated by regression. Callipyge and normal lambs did not differ for growth traits measured from birth to slaughter. Callipyge lambs produced 55.9% of live weight as chilled carcass weight compared with 51.7% for normal lambs at the same mean live weight of 48.32 kg. Lighter pelt, kidney-pelvic fat, and liver weights contributed to this advantage of callipyge lambs for dressing percentage (P < .001). Estimated accretion rates of carcass protein at the mean slaughter age were 12.5 and 10.2 g/d for callipyge and normal carcasses, respectively. Corresponding values for carcass fat were 35.2 and 42.1 g/d. Compositional differences in favor of callipyge carcasses were detected at constant values of slaughter age, carcass weight, and 12th-rib fat depth. Callipyge carcasses had 2.56 kg greater fat-free lean and 1.39 kg less fat than normal carcasses at the same mean age of 214.9 d (P < .001). The majority of these differences were established before the initial group was slaughtered and were maintained as age increased. Callipyge carcasses consisted of 24.3% fat and 71.3% fat-free lean, compared with 31.5 and 64.0% for normal carcasses at 25.6 kg of carcass weight. When evaluated at .49 cm of 12th-rib fat depth, callipyge lambs were 15.4 d older and produced 4.1 kg heavier carcasses with 4.3% less fat (P < .001). Effects of CLPG genotypic groups on carcass composition were greater than virtually all reported breed substitution effects. Use of the CLPG mutant allele in structured mating systems can dramatically increase production of lean lamb.     

Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene

Familial hyperaldosteronism type II (FH-II) is characterized by autosomal dominant inheritance and hypersecretion of aldosterone due to adrenocortical hyperplasia or an aldosterone-producing adenoma; unlike FH type I (FH-I), hyperaldosteronism in FH-II is not suppressible by dexamethasone. Of a total of 17 FH-II families with 44 affected members, we studied a large kindred with 7 affected members that was informative for linkage analysis. Family members were screened with the aldosterone/PRA ratio test; patients with aldosterone/PRA ratio greater than 25 underwent fludrocortisone/salt suppression testing for confirmation of autonomous aldosterone secretion. Postural testing, adrenal gland imaging, and adrenal venous sampling were also performed. Individuals affected by FH-II demonstrated lack of suppression of plasma A levels after 4 days of dexamethasone treatment (0.5 mg every 6 h). All patients had negative genetic testing for the defect associated with FH-I, the CYP11B1/CYP11B2 hybrid gene. Genetic linkage was then examined between FH-II and aldosterone synthase (the CYP11B2 gene) on chromosome 8q. A polyadenylase repeat within the 5'-region of the CYP11B2 gene and 9 other markers covering an approximately 80-centimorgan area on chromosome 8q21-8qtel were genotyped and analyzed for linkage. Two-point logarithm of odds scores were negative and ranged from -12.6 for the CYP11B2 polymorphic marker to -0.98 for the D8S527 marker at a recombination distance (theta) of 0. Multipoint logarithm of odds score analysis confirmed the exclusion of the chromosome 8q21-8qtel area as a region harboring the candidate gene for FH-II in this family. We conclude that FH-II shares autosomal dominant inheritance and hyperaldosteronism with FH-I, but, as demonstrated by the large kindred investigated in this report, it is clinically and genetically distinct. Linkage analysis demonstrated that the CYP11B2 gene is not responsible for FH-II in this family; furthermore, chromosome 8q21-8qtel most likely does not harbor the genetic defect in this kindred.