Offspring Genotypes Research Articles

Self- and Cross-Fertilization in the Solitary AscidianCiona savignyi

Solitary ascidians are hermaphrodites that release sperm and eggs simultaneously. However, many species are self-sterile, owing to a self/non-self recognition system operating at the outer surface of the chorion during sperm-egg interaction. In Ciona intestinalis, self-incompatibility is thought to have a genetic basis. Here, we report a survey of the self-fertilization potential of a Santa Barbara, California, population of Ciona savignyi, a close relative of C. intestinalis. We found that, in contrast to reports on C. intestinalis, C. savignyi is highly self-fertile. However, using two nonlethal recessive mutant strains, aimless (aim) and immaculate (imc), and a stable transgenic strain that expresses green fluorescent protein (GFP) in the notochord to follow offspring genotype, we demonstrate that non-self sperm outcompete self-sperm in fertilization competition assays. When the chorion was removed, both self- and non-self sperm performed equally well in the competition assay. Thus the non-self/self gamete recognition in C. savignyi is not absolute but relative, and is mediated by one or more components in the chorion. We discuss the significance of this finding in the context of natural populations in the wild, where individuals of C. savignyi are typically found growing in large groups that spawn in unison and where self-fertilization would be expected to be very rare.

Generation, characterization, and molecular cloning of theNoerg-1mutation of rhodopsin in the mouse

We performed genome-wide mutagenesis of C57BL/6J mice using the mutagen N-ethyl-N-nitrosourea (ENU) and screened the third generation (G3) offspring for visual system alterations using electroretinography and fundus photography. Several mice in one pedigree showed characteristics of retinal degeneration when tested at 12-14 weeks of age: no recordable electroretinogram (ERG), attenuation of retinal vessels, and speckled pigmentation of the fundus. Histological studies showed that the retinas undergo a photoreceptor degeneration with apoptotic loss of outer nuclear layer nuclei but visual acuity measured using the optomotor response under photopic conditions persists in spite of considerable photoreceptor loss. The Noerg-1 mutation showed an autosomal dominant pattern of inheritance in progeny. Studies in early postnatal mice showed degeneration to occur after formation of partially functional rods. The Noerg-1 mutation was mapped genetically to chromosome 6 by crossing C57BL/6J mutants with DBA/2J or BALB/cJ mice to produce an N2 generation and then determining the ERG phenotypes and the genotypes of the N2 offspring at multiple loci using SSLP and SNP markers. Fine mapping was accomplished with a set of closely spaced markers. A non-recombinant region from 112.8 Mb to 115.1 Mb was identified, encompassing the rhodopsin (Rho) coding region. A single nucleotide transition from G to A was found in the Rho gene that is predicted to result in a substitution of Tyr for Cys at position 110, in an intradiscal loop. This mutation has been found in patients with autosomal dominant retinitis pigmentosa (RP) and results in misfolding of rhodopsin expressed in vitro. Thus, ENU mutagenesis is capable of replicating mutations that occur in human patients and is useful for generating de novo models of human inherited eye disease. Furthermore, the availability of the mouse genomic sequence and extensive DNA polymorphisms made the rapid identification of this gene possible, demonstrating that the use of ENU-induced mutations for functional gene identification is now practical for individual laboratories.

PARENTAGE ANALYSIS OF THE CANYON MOUSE (PEROMYSCUS CRINITUS): EVIDENCE FOR MULTIPLE PATERNITY

Mating systems within the genus Peromyscus have traditionally been inferred from field observations of spatial relationships of males and females and from laboratory behavioral studies. The majority of species within Peromyscus are assumed to be promiscuous, but rarely have these conclusions been verified with molecular data. Genotypes constructed from 4 microsatellite loci were used to determine paternity in 10 litters of the canyon mouse (Peromyscus crinitus). We applied 3 criteria for paternity assignment: direct observation of paternal alleles, correlation of sampled male and offspring genotypes (mothers known) including spatial relationship data, and application of a likelihood estimator. Multiple paternity occurred in a minimum of 20% of the litters, yet we found no evidence that would indicate that any putative father sired 2 or more litters. Dispersal of males between the time of copulation and parturition was minimal (7.5–70 m) in most cases, but 1 male was captured in a rock outcropping separate from that of his sired litter (174 m). Our use of 3 different criteria allowed a greater number of male paternity assignments to be inferred than would have been possible when using software program CERVUS alone, and increased confidence in these results.

Evidence for biased use of sperm sources in wild female giant cuttlefish ( Sepia apama )

In species where females store sperm from their mates prior to fertilization, sperm competition is particularly probable. Female Sepia apama are polyandrous and have access to sperm from packages (spermatangia) deposited by males onto their buccal area during mating and to sperm stored in internal sperm-storage organs (receptacles) located below the beak. Here, we describe the structure of the sperm stores in the female's buccal area, use microsatellite DNA analyses to determine the genetic diversity of stored sperm and combine these data with offspring genotypes to determine the storage location of paternal sperm. The number of male genotypes represented in the sperm receptacles was significantly lower than that found among the spermatangia. Estimation of the volumes of sperm contained in the receptacles and the spermatangia were statistically comparable; however, paternal sperm were more likely to have come from spermatangia than from the sperm receptacles. These results confirm a genetic polyandrous mating system in this species and suggest that fertilization pattern with respect to the sperm stores used is not random.

Assessing Maternal Genetic Associations

In utero exposures, including maternal phenotypes, are potential risk factors for both early-onset and adult-onset diseases. Two alternative study designs use maternal genotypes at polymorphic loci as biomarkers of an offspring's in utero exposure: (1) a traditional case-control study with logistic regression analysis, in which cases, controls, and mothers of both types of subjects are genotyped; and (2) a case-parent triad study with log-linear analysis, in which cases and both parents are genotyped. We used computer simulations to compare the operating characteristics of the log-linear approach to case-parent triad data and the case-control approach for assessing relative risks (RRs) associated with maternal genotypes. For high-risk allele frequencies (chromosomal prevalence; f) between 0.20 and 0.75, both methods allowed for valid, unbiased estimates of maternal RRs. The case-parent triad approach, however, had 43% greater power, on average, than the case-control approach with an equal number of genotypes, and 13% greater power with an equal number of cases. For example, under dominant inheritance, to detect 2-fold maternal RRs with 200 (or 150) cases when allele prevalence is between 0.15 and 0.40, the case-parent triad and equal-genotype case-control designs had, on average, 87% and 62% power, respectively. As f approached 0 or 1, the power of both methods decreased sharply. The greater efficiency of case-parent triads may be due to the inclusion of paternal genotype information, which allows for independent tests of disease association with maternal or offspring genotypes. These results highlight one potential advantage of case-parent triad data in assessing maternal genetics as risk factors for offspring disease. We discuss these findings and other considerations between the 2 methodological approaches.

Power and Related Statistical Properties of Conditional Likelihood Score Tests for Association Studies in Nuclear Families with Parental Genotypes

SummaryBoth population based and family based case control studies are used to test whether particular genotypes are associated with disease. While population based studies have more power, cryptic population stratification can produce false‐positive results. Family‐based methods have been introduced to control for this problem. This paper presents the full likelihood function for family‐based association studies for nuclear families ascertained on the basis of their number of affected and unaffected children. The likelihood of a family factors into the probability of parental mating type, conditional on offspring phenotypes, times the probability of offspring genotypes given their phenotypes and the parental mating type. The first factor can be influenced by population stratification, whereas the latter factor, called the conditional likelihood, is not. The conditional likelihood is used to obtain score tests with proper size in the presence of population stratification (see also Clayton (1999) and Whittemore & Tu (2000)). Under either the additive or multiplicative model, the TDT is known to be the optimal score test when the family has only one affected child. Thus, the class of score tests explored can be considered as a general family of TDT‐like procedures. The relative informativeness of the various mating types is assessed using the Fisher information, which depends on the number of affected and unaffected offspring and the penetrances. When the additive model is true, families with parental mating type Aa×Aa are most informative. Under the dominant (recessive) model, however, a family with mating type Aa×aa(AA×Aa) is more informative than a family with doubly heterozygous (Aa×Aa) parents. Because we derive explicit formulae for all components of the likelihood, we are able to present tables giving required sample sizes for dominant, additive and recessive inheritance models.

Power and Related Statistical Properties of Conditional Likelihood Score Tests for Association Studies in Nuclear Families with Parental Genotypes

Both population based and family based case control studies are used to test whether particular genotypes are associated with disease. While population based studies have more power, cryptic population stratification can produce false-positive results. Family-based methods have been introduced to control for this problem. This paper presents the full likelihood function for family-based association studies for nuclear families ascertained on the basis of their number of affected and unaffected children. The likelihood of a family factors into the probability of parental mating type, conditional on offspring phenotypes, times the probability of offspring genotypes given their phenotypes and the parental mating type. The first factor can be influenced by population stratification, whereas the latter factor, called the conditional likelihood, is not. The conditional likelihood is used to obtain score tests with proper size in the presence of population stratification (see also Clayton (1999) and Whittemore & Tu (2000)). Under either the additive or multiplicative model, the TDT is known to be the optimal score test when the family has only one affected child. Thus, the class of score tests explored can be considered as a general family of TDT-like procedures. The relative informativeness of the various mating types is assessed using the Fisher information, which depends on the number of affected and unaffected offspring and the penetrances. When the additive model is true, families with parental mating type Aa x Aa are most informative. Under the dominant (recessive) model, however, a family with mating type Aa x aa(AA x Aa) is more informative than a family with doubly heterozygous (Aa x Aa) parents. Because we derive explicit formulae for all components of the likelihood, we are able to present tables giving required sample sizes for dominant, additive and recessive inheritance models.

Covariate adjustment in family‐based association studies

Family-based tests of association between a candidate locus and a disease evaluate how often a variant allele at the locus is transmitted from parents to offspring. These tests assume that in the absence of association, an affected offspring is equally likely to have inherited either one of the two homologous alleles carried by a parent. However, transmission distortion was documented in families in which the offspring are unselected for phenotype. Moreover, if offspring genotypes are associated with a risk factor for the disease, transmission distortion to affected offspring can occur in the absence of a causal relation between gene and disease risk. We discuss the appropriateness of adjusting for established risk factors when evaluating association in family-based studies. We present methods for adjusting the transmission/disequilibrium test for risk factors when warranted, and we apply them to data on CYP19 (aromatase) genotypes in nuclear families with multiple cases of breast cancer. Simulations show that when genotypes are correlated with risk factors, the unadjusted test statistics have inflated size, while the adjusted ones do not. The covariate-adjusted tests are less powerful than the unadjusted ones, suggesting the need to check the relationship between genotypes and known risk factors to verify that adjustment is needed. The adjusted tests are most useful for data containing a large proportion of families that lack disease-discordant sibships, i.e., data for which multiple logistic regression of matched sibships would have little power. Software for performing the covariate-adjusted tests is available at http://www.stanford.edu/dept/HRP/epidemiology/COVTDT.

Genetic variance of mating frequency in the honeybee (Apis mellifera L.)

The genetic variance of queen mating frequency was studied in honeybees (Apis mellifera carnica). Worker offspring (N = 966) of 28 naturally mated half sister-queens (r = 0.25) from seven unrelated breeding lines were genotyped at four DNA microsatellites. The mating frequencies of the queens were derived from the offspring genotypes. The number of observed matings per queen ranged from 10 to 28 with an average of 17.32 ± 1.10 (number of estimated matings: 24.94 ± 2.51; number of effective matings: 20.09 ± 1.73). Half-sib analyses of the breeding lines were used to estimate heritability. Heritability was h2 = 0.449 ± 0.135 for the estimated number of matings and h2 = 0.262 ± 0.103 for the number of effective males, which are both significantly different from zero. We conclude that a high genetic variance for polyandry in honeybees can be favored by balanced selection between individual queen and colony level.

Common polymorphism in H19 associated with birthweight and cord blood IGF-II levels in humans

BackgroundCommon genetic variation at genes that are imprinted and exclusively maternally expressed could explain the apparent maternal-specific inheritance of low birthweight reported in large family pedigrees. We identified ten single nucleotide polymorphisms (SNPs) in H19, and we genotyped three of these SNPs in families from the contemporary ALSPAC UK birth cohort (1,696 children, 822 mothers and 661 fathers) in order to explore associations with size at birth and cord blood IGF-II levels.ResultsBoth offspring's and mother's H19 2992C>T SNP genotypes showed associations with offspring birthweight (P = 0.03 to P = 0.003) and mother's genotype was also associated with cord blood IGF-II levels (P = 0.0003 to P = 0.0001). The offspring genotype association with birthweight was independent of mother's genotype (P = 0.01 to P = 0.007). However, mother's untransmitted H19 2992T allele was also associated with larger birthweight (P = 0.04) and higher cord blood IGF-II levels (P = 0.002), suggesting a direct effect of mother's genotype on placental IGF-II expression and fetal growth. The association between mother's untransmitted allele and cord blood IGF-II levels was more apparent in offspring of first pregnancies than subsequent pregnancies (P-interaction = 0.03). Study of the independent Cambridge birth cohort with available DNA in mothers (N = 646) provided additional support for mother's H19 2992 genotype associations with birthweight (P = 0.04) and with mother's glucose levels (P = 0.01) in first pregnancies.ConclusionThe common H19 2992T allele, in the mother or offspring or both, may confer reduced fetal growth restraint, as indicated by associations with larger offspring birth size, higher cord blood IGF-II levels, and lower compensatory early postnatal catch-up weight gain, that are more evident among mother's smaller first-born infants.

A Monte Carlo Approach for Estimation of Haplotype Probabilities in Half-Sib Families

The objective of this work was to propose an algorithm (HAPROB) to estimate haplotype probabilities for genotyped members of half-sib families for which parents lacked genotypic information. The algorithm had 2 basic steps. First, a Monte Carlo-based approach was used to estimate haplotype probabilities for sires conditional upon offspring genotypes and population allelic frequencies, and then offspring-haplotype probabilities were estimated conditional upon sire probabilities and population frequencies. The 2 steps were alternated iteratively until estimates of population frequencies were essentially unchanged. Simulation was used to evaluate effects of the number of Monte Carlo cycles on the accuracy of the reconstructed haplotypes. Fifty thousand cycles was found to be sufficient for the haplotype configurations considered. Accuracy of the algorithm was compared with that obtained by the public domain SIMWALK2 software. Predictions of the most likely haplotype configurations are produced by SIM-WALK2, but no estimates of probability are given. The accuracy of the current approach was comparable to that obtained from SIMWALK2. The proportions of times that haplotypes were reconstructed correctly were 87.0 and 92.4% (sires and offspring) for HAPROB vs. 87.5 and 91.5% for SIMWALK2. Effects of family size on accuracy of reconstruction were examined. Accuracy of reconstruction was only about 4% for sires with 2 offspring, but accuracy among the offspring themselves was 65%. Accuracy increased quickly as family size increased and reached 100% for sires with 30 offspring. Maximum accuracy for offspring was about 96%. Estimates of haplotype probabilities produced can be used in regression analyses to estimate effects of haplotypes on quantitative phenotypes.

Mating patterns in a hybrid zone of fire-bellied toads (Bombina): inferences from adult and full-sib genotypes

We present two novel methods to infer mating patterns from genetic data. They differ from existing statistical methods of parentage inference in that they apply to populations that deviate from Hardy-Weinberg and linkage equilibrium, and so are suited for the study of assortative mating in hybrid zones. The core data set consists of genotypes at several loci for a number of full-sib clutches of unknown parentage. Our inference is based throughout on estimates of allelic associations within and across loci, such as heterozygote deficit and pairwise linkage disequilibrium. In the first method, the most likely parents of a given clutch are determined from the genotypic distribution of the associated adult population, given an explicit model of nonrandom mating. This leads to estimates of the strength of assortment. The second approach is based solely on the offspring genotypes and relies on the fact that a linear relation exists between associations among the offspring and those in the population of breeding pairs. We apply both methods to a sample from the hybrid zone between the fire-bellied toads Bombina bombina and B. variegata (Anura: Disco glossidae) in Croatia. Consistently, both approaches provide no evidence for a departure from random mating, despite adequate statistical power. Instead, B. variegata-like individuals among the adults contributed disproportionately to the offspring cohort, consistent with their preference for the type of breeding habitat in which this study was conducted.

Calcineurin A-α But Not A-β Is Required for Normal Kidney Development and Function

Calcineurin is an important signaling molecule in the kidney and may be involved in a variety of processes. The phosphatase subunit of calcineurin (CnA) has three isoforms, alpha, beta, and gamma. In this study, we investigated the effect of loss of calcineurin A-alpha (CnA-alpha) or calcineurin A-beta (CnA-beta) on the development and function of the kidney. Total calcineurin expression and activity was significantly reduced in whole kidney homogenates from both CnA-alpha -/- and CnA-beta -/- mice. Kidneys of CnA-beta -/- mice appear normal and the mice develop with no phenotypic abnormalities. In contrast, kidneys of CnA-alpha -/- animals fail to fully develop. In particular, postnatal maturation of the nephrogenic zone (NZ) is defective. Within the NZ, glomeruli also fail to mature and lack mesangial cells. In addition to alterations in development, there is an absence of proliferation and an increase of cell death in the NZ with loss of CnA-alpha. Finally, increased collagen deposition is observed and serum creatinine levels are significantly increased in CnA-alpha -/- animals compared to wild-type littermates, indicating that kidney function is impaired. In summary, absence of CnA-alpha but not CnA-beta leads to a defect in normal maturation of the NZ and glomeruli, alterations in the cell cycle, and impaired kidney function.

Matesoft: a program for deducing parental genotypes and estimating mating system statistics in haplodiploid species

AbstractWith the advent of sophisticated genetic markers, studies on mating systems and reproductive apportionment have become increasingly feasible. In particular, paternity analyses in haplodiploid species have gained in power as hemizygous paternal genotypes allow maternal and paternal genotypes to be directly inferred from offspring genotypes. The computer program matesoft offers both newly developed algorithms for inferring maternal and paternal genotypes, and integrated estimation and correction procedures for calculating mating frequency statistics. Standard data are offspring genotypes of male‐haplodiploid organisms, including social Hymenoptera.

Maternal MTHFR interacts with the offspring's BCL3 genotypes, but not with TGFA, in increasing risk to nonsyndromic cleft lip with or without cleft palate.

The 677 C --> T polymorphism in the 5-10 methylenetetrahydrofolate reductase (MTHFR) gene has been associated with nonsyndromic cleft lip with or without cleft palate (CL/P) in some populations, but not others. Previous studies (ie, case-control and transmission disequilibrium tests (TDT)) in Brazilian families with CL/P have been unable to replicate this putative association. However, our group observed a lower proportion of CT heterozygotes among the mothers of CL/P probands, suggesting that the maternal genotype for this polymorphism might influence predisposition to CL/P. In order to further examine this issue, we performed a case-control study of the 677 C --> T/MTHFR polymorphism in families with CL/P ascertained in two regions of Brazil: 172 from São Paulo (SP) and 252 from Ceará (CE). The control samples included 243 individuals from SP and 401 from CE. TDT was carried out in 102 patients with CL/P and their parents. No evidence of an association was observed between the 677 C --> T/MTHFR polymorphism and CL/P using the case-control design, while borderline significance was obtained with the TDT (P=0.055). We have also looked for an interaction between maternal MTHFR genotypes and the propositi offspring's genotypes at two candidate susceptibility loci for CL/P, TGFA and BCL3. Interestingly, we observed an interaction between the maternal MTHFR and offspring's BCL3 genotypes (OR: 2.3; 95% CI: 1.1-4.8; P=0.03) but not with the offspring's TGFA genotypes. Therefore, our results reinforce the idea that the maternal MTHFR genotype plays a significant role in susceptibility to CL/P, but its teratogenic effect depends on the genotype of the offspring.

Do seed mass and family affect germination and juvenile performance in Knautia arvensis? A study using failure-time methods

Germination and seedling establishment are vulnerable stages in the plant life cycle. We investigated how seed mass and family (progeny origin) affect germination and juvenile performance in the grassland herb Knautia arvensis. Seeds were produced by cross-pollination by hand. The fate of 15 individually weighed seeds from each of 15 plants was followed during a 3-month growth chamber experiment. Progeny origin affected germination, both through seed mass and as an independent factor. Two groups of progenies could be distinguished by having rapid or delayed germination. The two groups had similar mean seed masses, but a positive relationship between seed mass and germination rate could be established only among the rapidly germinating progenies. These biologically relevant patterns were revealed because timing of germination was taken into account in the analyses, not only frequencies. Time-to-event data were analysed with failure-time methods, which gave more stable estimates for the relation between germination and seed mass than the commonly applied logistic regression. Progeny origin and seed mass exerted less impact on later characters like juvenile survival, juvenile biomass, and rosette number. These characters were not affected by the timing of germination under the competition-free study conditions. The decrease in the effect of progeny origin from the seed and germination to the juvenile stages suggests that parental effects other than those contributing to the offspring genotype strongly influenced the offspring phenotype at the earliest life stages. Further, the division of progeny germination patterns into two fairly distinct groups indicates that there was a genetic basis for the variation in stratification requirements among parental plants. Field studies are needed to elucidate effects of different timing of germination in the seasonal grasslands that K. arvensis inhabits.

An exact maternal-fetal genotype incompatibility (MFG) test.

The maternal-fetal genotype incompatibility (MFG) test can be used for a variety of genetic applications concerning disease risk in offspring including testing for the presence of alleles that act directly through offspring genotypes (child allelic effects), alleles that act through maternal genotypes (maternal allelic effects), or maternal-fetal genotype incompatibilities. The log-linear version of the MFG model divides the genotype data into many cells, where each cell represents one of the possible mother, father, and child genotype combinations. Currently, tests of hypotheses about different allelic effects are accomplished by an asymptotic MFG test, but it is unknown if this is appropriate under conditions that produce small cell counts. In this report, we develop an exact MFG test that is based on the permutation distribution of cell counts. We determine by simulation the type I error and power of both the exact MFG test and the asymptotic MFG test for four different biologically relevant scenarios: a test of child allelic effects in the presence of maternal allelic effects, a test of maternal allelic effects in the presence of child allelic effects, and tests of maternal-fetal genotype incompatibility with and without child allelic effects. These simulations show that, in general, the exact test is slightly conservative whereas the asymptotic test is slightly anti-conservative. However, the asymptotic MFG test produces significantly inflated type I error rates under conditions with extreme null allele frequencies and sample sizes of 75, 100, and 150. Under these conditions, the exact test is clearly preferred over the asymptotic test. Under all other conditions that we tested, the user can safely choose either the exact test or the asymptotic test.

Maternal age affects offspring lifespan of the seed beetle,Callosobruchus maculatus

SummaryOffspring from older parents often have shorter adult lifespans than offspring of younger mothers. We examine the effects of offspring genotype, maternal age and paternal age on offspring survival, development and adult lifespan in the seed beetle,Callosobruchus maculatus.Females took about a quarter of a day longer to develop from an egg to an adult and lived ≈7 days longer than males. Mortality patterns were best described by a logistic mortality model, and all three model parameters differed significantly between the sexes; females had a higher baseline mortality rate than males but the mortality rate increased more slowly in females than in males. Females also showed a delay, relative to males, in the age at which mortality became age‐dependent.The proportion of eggs that hatched and larval survivorship both declined with increasing maternal age, while egg‐to‐adult development time increased substantially. Contrary to the pattern observed in many other organisms, offspring of older mothers livedlongerthan offspring of younger mothers, even after controlling for heterogeneity among families. There was no evidence that paternal age affected any offspring traits.The effect of maternal age on offspring lifespan was greater for male offspring than for female offspring (consistent with the general observation that the genetic and environmental factors affecting lifespan differ between the two sexes) and varied among sire families (indicating that offspring genotype mediated the non‐genetic effect of maternal age on lifespan).

Normal spermatogenesis and fertility in germ cell-specific genomic androgen receptor knockout mice

Objective: The purpose of the present study is to generate the seprmatocyte specific androgen receptor knock out (ARKO) mice using cre-lox strategy and to study its influence on spermatogenesis. Design: A tissue-specific knock-out animal model. Materials and Methods: Previous, we have generated a strain of mice carrying a fragment of lox sequence within the androgen receptor genome (flox-AR). In the present study, we mated the flox-AR mice with a mice carrying cre recombinase driven by spermatocyte specific promoter synaptonemal complex protein 1 (Sycp1-Cre mice). Since Sycp1 is only expressed at the leptotene-zygotene stage of spermatocyte, the generated Sycp1-ARKO male mice lost androgen receptor at the process of spermatogenesis after leptotene-zygotene stage. We compared the wild type (wt) and the Sycp1-ARKO mice on the fertility, AR expression, sperm count and histology of seminiferous tubules to determine how the spermatogenensis was influenced. The efficiency of the knock-out is confirmed by checking the genotypes of female offspring from the Sycp1-ARKO fathers and the wt C57BL/6J mothers. Results: Histology analyses indicate that each stage of spermatogenesis is normal and the expression of AR in Sertoli, Leydig, and peritubular cells is unaffected in Sycp1-ARKO mice. Sperm count and motility in epididymis from Sycp1-ARKO are similar to that of the wt siblings. The overall knock-out efficiency is 78%. However, 3 of 4 Sycp1-ARKO mice show 100% efficiency. Conclusion: The results suggest that the expression of androgen receptor in the male germ cells beyond the spermatocyte stage is redundant for the sperm maturation.

Placental genes and breast cancer: can the offspring's or father's genotypes predict mother's risk?

Half of the placental genes to which a woman is exposed during pregnancy come from her mating partner. Placental hormones, especially human chorionic gonadotropin and human placental lactogen, are considered to mediate the protective effects of full-term pregnancy and lactation on breast cancer risk. In this paper, variants in a woman's placental human chorionic gonadotropin or human placental lactogen genes, which are easily measurable through her offspring's genotypes, are associated with her breast cancer risk. If this hypothesis is true it would indicate that genotype of a woman's mating partner can affect her breast cancer risk and that offspring's genotype may be useful in predicting such risk. Because the placenta produces a wide range of hormones and enzymes (in addition to human chorionic gonadotropin and human placental lactogen), results supporting this hypothesis could open new dimensions to genetic research for diseases beyond breast cancer (including gynecologic tumors and reproductive and pregnancy-related disorders).