Haptoglobin-ABO interaction: a possible explanation for the excess of Hp 1 among offspring of ABO incompatible matings.

The Hp1 frequency among ABO phenotypes varies in the Hutterite population as follows: O less than A less than B less than AB. Within group O, the Hp1 frequency is significantly lower than the Hp1 frequency among the other groups combined. The Hp1 frequencies among ABO genotypes, known by means of family pedigrees, vary as follows: OO less than AO less than BO less than AB less than AA less than BB. This holds for both main subjects of this isolate, although they have been reproductively isolated since World War I. The higher Hp1 frequency among type A, B, and AB individuals explains the observation of the higher Hp1 frequencies found among H-leut offspring who are incompatible with their mothers (mainly AO offspring of OO mothers) compared to offspring from the same matings who are compatible with their mothers.     

Maternal-fetal interaction in the ABO system: a comparative analysis of healthy mothers and couples with recurrent spontaneous abortion suggests a protective effect of B incompatibility.

We investigated the possible differential effects of A and B blood group materno-fetal incompatibility on human fertility through a comparative analysis of couples with recurrent spontaneous abortion (RSA) and healthy mothers. ABO phenotype was determined in 5180 healthy mothers and their newborn babies from the population of Sassari (Sardinia) and in 1359 healthy puerperae (women who have just given birth) from the population of Rome. Mother-newborn joint ABO distribution in healthy mothers was compared with wife-husband joint ABO distribution in RSA couples. Distortions from expected distribution were evaluated by symmetry analysis. In both RSA couples and healthy mothers significant deviation from expected symmetry patterns were observed. Deviations in RSA are in the opposite direction to those observed in healthy puerperae. The most important difference observed concerned the symmetric joint phenotypes mother (women) A/infant (husband) B (B incompatible) and mother (women) B/infant (husband) A (A incompatible). A low number of B incompatible in RSA couples and a high number of B incompatible in healthy mothers was observed. The phenomenon is much more evident in women aged 24-28 years, a period of maximum fecundity. It is possible that the presence of anti-B immunoglobulin in the mother might have a protective effect against fetal loss in some cases of mother-infant ABO incompatibility.     

Segregation distortions of the ABO and Rh systems in malformed newborns

This study compares the segregation of the ABO and Rh systems between malformed newborns and a control group with two purposes: (1) to evaluate the participation of genetic factors associated with these blood groups in the production of congenital malformations, and (2) to prove, indirectly, the existence of reproductive losses associated with congenital malformations. The newborns and their mothers were typed for ABO and Rh groups. Gene frequencies were similar in malformed and control newborns. In the female malformed newborns, an excess of O-B pairs and a deficit of B-B pairs in the ABO system, and an excess of Rh(-)-Rh- pairs in the Rh system were found.     

Dominant role of host selective pressure in driving hepatitis C virus evolution in perinatal infection

The dynamics of the genetic diversification of hepatitis C virus (HCV) populations was addressed in perinatal infection. Clonal sequences of hypervariable region 1 of the putative E2 envelope protein of HCV were obtained from four HCV-infected newborns (sequential samples spanning a period of 6 to 13 months after birth) and from their mothers (all samples collected at delivery). The data show that the variants detected between birth and the third month of life in samples from the four newborns were present in the HCV populations of their mothers at delivery. In the newborns, a unique viral variant (or a small group of closely related variants) remained stable for weeks despite active viral replication. Diversification of the intrahost HCV population was observed 6 to 13 months after birth and was substantially higher in two of the four subjects, as documented by the intersample genetic distance (GD) (P = 0.007). Importantly, a significant correlation between increasing GD and high values for the intersample K(a)/K(s) ratio (the ratio between anoffymous and synonymous substitutions; an index of the action of selective forces) was observed, as documented by the increase of both parameters over time (P = 0.01). These data argue for a dominant role of positive selection for amino acid changes in driving the pattern of genetic diversification of HCV populations, indicate that the intrahost evolution of HCV populations is compatible with a Darwinian model system, and may have implications in the designing of future antiviral strategies.     

Genetic mechanism of blood group (ABO)-expression

It has generally been believed that human blood group ABO is controlled by allelic ABO genes. However, this hypothesis has not yet been experimentally proven, and other possibilities such as the non-allelic gene model and the regulatory gene model for ABO locus have also been proposed. The genetic mechanisms of many unusual blood group expressions remain unanswered. Purification of human blood group N-acetylgalactosyltransferase (A-enzyme) which synthesizes A-substance, and blood group galactosyltransferase which is responsible for synthesis of B-substance, allows us to resolve these problems from an immuno-biochemical approach. It was found that rabbit antibody against-A-enzyme completely neutralized not only A-enzyme but also B-enzyme activity. Moreover, plasma from blood type O subjects contained an enzymatically inactive but immunologically cross-reactive material (CRM). Plasma from heterozygous AO and BO subjects also contained CRM, but plasma from homozygous AA and BB subjects did not contain CRM. These facts led us to conclude that the ABO genes are allelic in the strict sense, refuting other genetic models for ABO locus. Genotypes of phenotype A and B subjects can be unequivocally determined by examining the presence or absence of CRM in their plasma. Mechanism of the unusual blood group inheritance of Cis-AB (i.e., AB and/or O childbirth from AB X O parent) was elucidated by examining properties of the A and B enzymes, CRM in their plasma, and separation of active enzymes and CRM by affinity chromatography. It became clear that Cis-AB expressions in one family was due to unequal chromosomal crossing-over producing a single chromosome with the genes for A and B enzymes. In contrast, in the other two unrelated families, the Cis-AB expression was due to a structural mutation in A or B gene producing a single abnormal enzyme which was capable of transferring both GalNAc and Gal to H-substance. Mechanism of very weak B expression in a family with A1Bm character was studied. Plasma enzyme activity and kinetic characteristics of B-enzyme from the subjects was not different from that of normal. However, the A1Bm red cells contained a large amount of unoccupied H-sites which can be galactosylated in vitro and become B active. Examination of membrane components by isoelectric focussing revealed that blood group components of the A1Bm membranes were distinctively different from that of the usual membranes. Consequently, the weak B expression is not due to direct mutation of ABO locus, but due to a secondary consequence of genetic abnormality of a membrane component (or components) associated with blood group substances.     

Abo blood groups and completed reproductive performance of rural Haryanavi couples: analysing measures of selection intensities

The possible differential effects of ABO blood group materno-paternal (fetal) incompatibility on completed reproductive performance were investigated on a sample of 100 couples (100 fathers and 100 mothers) from three villages in the Jind district of Haryana state, India. The average number of live births per mating couple was slightly higher for the incompatible matings (5.32) than the compatible ones (5.05). This advantage was offset by higher postnatal mortality in the former. Consequently, the average number of living children in the compatible matings (4.64) was higher than in the incompatible ones (4.18). With reference to individual ABO matings, the index of relative fertility (Irf) was the highest in A x AB followed by B x A type of incompatible matings. No decrease in live births in O x A and O x B incompatible matings was observed compared with their reciprocal compatible ones, i.e. A x O and B x O matings, as has been hypothesized in previous studies. The total pregnancy wastage was substantially higher in ABO-incompatible matings (24.59%) than compatible matings (8.45%). About 71% of the postnatal deaths took place within one year of the birth in the case of incompatible matings compared with 50% in the case of compatible matings. The study supports the hypothesis that selection is operative at the ABO locus as revealed by the measures of selection intensity. The loss of fitness in the present sample was associated with differential mortality. There were no differences in the proportions of average number of male live births in the compatible (0.55) and incompatible matings (0.58). However, in the individual mating types, there was some evidence of higher or lower proportions of male live births.     

Sex ratio in Down syndrome. Studies in patients with confirmed trisomy 21

Male to female ratio (sex ratio, SR) for 1,329 liveborns with Down syndrome and for 178,160 newborns from the general population of St. Petersburg, Russia was determined as a function of a mother age. Male prevalence (an overall SR of 1.24) was found in children with all trisomy 21 variants except the cases with mosaicism (the ratio of 0.88). The most expressed male predominance was determined in children of mothers aged 20-24 years, where SR was 1.73 in the total group (p = 0.00003) and 1.61 in the cases with free trisomy (p = 0.0007). Some hypotheses concerning the male accumulation in this group are discussed including a suggestion that the SR deviations from the population value 1.06 might be due to different contribution of paternal chromosomal non-disjunction during spermatogenesis.     

Sexual orientation, handedness, sex ratio and fetomaternal tolerance-rejection

Fraternal birth order (FBO) appears as a prenatal cause of 15% of homosexual males (gays) through mnemonic maternal anti-male factors. Non-right-handed men seem to be protected from homosexuality. Four hypotheses are proposed: (1) androgenic factors of non-right-handedness neutralize anti-male factors; (2) non-right-handedness and homosexuality are lethal or produce mental impairment; (3) non-right-handed male embryos are insensitive to anti-male factors; (4) mothers of non-right-handed fetuses do not produce anti-male factors. Studies of the sex ratio (SR) of older and younger siblings show: (1) a significant heterogeneity in the SR of siblings of right or non-right handed heterosexual men and women; (2) lesbians are born among siblings with high SR; (3) siblings of right-handed gays show a higher SR than non-right-handed gays that present a low SR. Based on our discovery of maternal tolerance-rejection processes, associated with genetic systems (ABO, Rh), where zygotes or embryos different from their mother induce better pregnancy and maternal tolerance than do those that share antigens with their mothers, I propose a new explanation for sexual relationships, sexual orientation, handedness and sibling SR. Lesbian embryos could induce tolerance from mothers with anti-female factors. Non-right-handedness could induce maternal tolerance, or change the maternal compatibility of "gay" embryos. Alternatively, gay embryos could be poor inducers of maternal tolerance towards male traits.     

ABO hemolytic disease of the newborn as a selection mechanism at the ABO locus

Data from the period 1951 to 1967 were collected from the records at the Milwaukee Blood Center on 380 cases of ABO hemolytic disease to determine if ABO incompatibility may be regarded as a selection mechanism at the ABO locus. In comparison with infants of ABO compatible parents the affected infants had significantly lower hemoglobin and hematocrit values and higher bilirubin concentrations. Forty-eight percent of the affected showed a positive direct antiglobulin test, 81% showed increased numbers of reticulocytes and 92% had spherocytosis. Since affected infants are considered to be in grave danger when high concentrations of bilirubin are present it is significant that 169 individuals (44%) required exchange transfusions. Compared with the number of live births in Milwaukee for the same period this represents a frequency of one in every 1,654 live births so that ABO incompatibility may be regarded as an important mechanism of natural selection. Since it was found that 98.7% of the mothers of the affected infants are of blood group O, the affected infants are therefore heterozygous (AO or BO) and selection due to ABO incompatibility would have its greatest effect upon the lowest allele frequencies in a population.     

The influence of mother's active smoking during pregnancy on body mass index of newborns

Many investigations have noted bad influence of smoking during pregnancy. In the present article, the influence of mothers smoking during pregnancy on the body mass index (BMI), birth weight and birth length are examined. This retrospective research included 219 children: Group I: 109 children from rural area of east Slavonia (born in General Hospital-Vinkovci) and group II: 110 children from industrial area (born in Zagreb). The questioned subjects were divided into two groups depending on mothers smoking during pregnancy: newborns of mothers who didn't smoke during pregnancy (subgroup A) and newborns of mother who did smoke 10 or more cigarettes per day during pregnancy (subgroup B). Anthropometric parameters (BMI, birth length and birth weight) in newborns of non-smoking mothers were statistically higher (p < 0.05) than in newborns of smoking mothers. Moderate correlation between birth length and birth weight in newborns of non-smoking and smoking mothers from rural area and from non-smoking mothers in urban area was statistically significant, but correlation in the group in newborns of smoking mothers from Zagreb was not statistically significant. Results of this research show that smoking during pregnancy significantly influences the birth weight and birth length. Further investigation is needed, to investigate the lack of correlation between the birth length and birth weight in newborns of smoking mothers from industrial city.     

Micronuclei levels in mothers and their newborns from regions with different types of air pollution

The aim of this study was to analyze genetic damage in human lymphocytes measured using automated image analysis of micronuclei (MN) in a group of 178 mothers and their newborns from two locations in the Czech Republic. The concentrations of benzo[a]pyrene (B[a]P), particulate matter of aerodynamic diameter <2.5 μm (PM2.5) and benzene were measured by stationary monitoring in the winter season of 2008/2009 in the capital city of Prague and in Ceske Budejovice, a regional city in a rural area. The 3-month mean concentration of B[a]P before delivery was lower in Prague in comparison with Ceske Budejovice: 1.9 ± 0.5ng/m3 vs. 3.2 ± 0.2ng/m3 (p<0.001). The opposite trend was found for PM2.5 and benzene: 27.0 ± 2.5μg/m3 and 2.5 ± 0.5μg/m3 vs. 24.5 ± 0.7μg/m3 and 2.1 ± 0.8μg/m3 (p<0.001) for Prague vs. Ceske Budejovice, respectively. The average age of the mothers was 31 years (range, 18-49 years). The frequencies of MN per 1000 binucleated cells were 8.35 ± 3.06 vs. 6.47 ± 2.35 (p<0.001) for mothers from Prague and Ceske Budejovice, respectively, and 2.17 ± 1.32 vs. 3.82 ± 2.43 (p<0.001) for newborns from Prague and Ceske Budejovice, respectively. Other factors, including vitamin intake, exposure to tobacco smoke, body mass index (BMI) before pregnancy, the education level of the mothers and the impact of the mothers' and fathers' ages were analyzed in our study. The results suggest that the different sensitivity of the study groups to various mixtures of carcinogenic pollutants could be affected by significant differences in lifestyle factors. Possible higher genetic damage was analyzed in newborns of smoking mothers, and the birth weight of this group was 7.4% lower (p<0.05) in comparison with the newborns of nonsmoking mothers. No impact of the age of the mothers or fathers on MN frequency in the newborns was observed.     

Concentration and avidity of anti-tetanus antibodies in mother-infant pairs: Relation to immunization time

Abstract The concentration and avidity of anti-tetanus antibodies in two groups of mother-infant pairs were compared. Mothers immunized during pregnancy and their newbons (group A) had significantly higher antibody concentrations than mothers immunized at least a year before their last pregnancy and their newborns (group B) as measured by an indirect enzyme immunoassay (EIA) procedure. Antibody avidity of samples was measured by an inhibition EIA technique and urea denaturation test. Although antibody avidity was higher in group B, the differences were not significant. These findings may represent a secondary antibody response to a protein antigen, when considering that all mothers in both groups had received a primary tetanus vaccination during childhood. In mothers with a history of primary tetanus immunization, a single booster dose of tetanus toxoid during pregnancy is enough to induce protective levels of antibodies with reasonably high avidity in both mother and newborn.     

Population genetic study of Russian cosmonauts and test subjects: genetic demographic parameters and immunogenetic markers

Genetic demographic characteristics and immunogenetic markers (blood groups ABO, Rhesus, MNSs, P, Duffy, Kidd, and Kell) have been studied in a group of 132 Russian cosmonauts and test subjects (CTSG). Analysis of pedigrees has shown a high exogamy in the preceding generations: almost half of the subjects have mixed ethnic background. According to the results of genetic demographic analysis, a sample from the Moscow population was used as control group (CG). Comparison between the CTSG and CG has demonstrated significant differences in genotype frequencies for several blood group systems. The CTSG is characterized by a decreased proportion of rare interlocus genotypic combinations and an increased man heterozygosity. Analysis of the distributions of individual heterozygosity for loci with codominant expression of alleles has shown that highly heterozygous loci are more frequent in the CTSG. Taking into account that the CTSG has been thoroughly selected from the general population, it is concluded that heterozygosity is related to successful adaptation to a space flight.     

Reproductive behavior and Down syndrome

Coital rates and contraception practice were investigated in mothers of 160 newborns with Down syndrome (DS) in comparison with the same aged (+/- 1 year) mothers of 160 healthy newborns. A considerable lowering of sexual activity is typical for parents, especially young ones, of children with DS. No relationship between parental sexual behavior and maternal hormonal dysfunction was found. Study on children sex ratio (SR) in relation to parental sexual activity revealed that the prevalence of boys in the DS children was due to the excess of boys (SR = 1.85) in the small group of children from sexually active couples. These data are discussed as evidence of association of a high coital rate with chromosome malsegregation in spermatogenesis.     

Ecology of serogroup B streptococci in maternity hospitals (preliminary report)

Materials on the study of the colonization of newborns, their mothers and the medical staff of a maternity hospital by group B streptococci are presented. These streptococci were isolated from 26.3% of newborns, 19.6% of puerperae and 14.7% of the staff members. Group B streptococci were found to colonize different loci in newborns (the fauces, the nose, the umbilical cord, the ears, feces) and their mothers (the fauces, the vagina, the perianal fold, milk, the skin around the nipples, amniotic fluid, the umbilical cord). The serological typing of streptococci, isolated simultaneously from newborns and their mothers, suggested the presence of two possibilities of infecting the newborns with these microorganisms: (1) from their mothers and (2) from other newborns or members of the hospital staff during the stay in the maternity hospital.     

Is delayed childbearing changing gene frequencies in Western populations?

Experimental data and clinical observations suggest that delaying childbearing influences the biology of the mother-fetus relationship, with a negative effect on fetal development and predisposition to severe diseases such as type 1 diabetes. We reason that advanced maternal age may influence intrauterine selection, favoring genotypes that are more adapted to the intrauterine environment of less young women. In the present study we have investigated the relationship of maternal age to HP genotype and PGM1-Rh area (chromosome 1) that have been previously found to be associated with fertility and developmental parameters. HP phenotype was determined in 679 consecutive puerperae from the population of central Italy. PGM1 phenotype and Rh C phenotype were determined in 222 puerperae and 200 newborns. The HP 1,1 phenotype decreases and the HP 2,2 phenotype increases with maternal age. The proportion of phenotypes carrying both the Rh C and PGM1*1 alleles is much higher in puerperae older than 36 years than in puerperae of age 22 years. The frequency of the PGM1*1-Rh C haplotype increases and the frequency of the PGM1*2-Rh C haplotype decreases with maternal age. The changes in these genetic systems with advancing maternal age are similar in mothers and newborns. The delay of childbearing age, associated in Western countries with the fertility transition in addition to detrimental effects on intrauterine development and increased susceptibility to severe disorders, could bring about changes in the genetic composition of a population.     

Distribution of ABO blood groups and other genetic markers in mothers of infants with congenital malformations

The distribution of ABO and Rh (antigen D) blood groups and of serum albumin, haptoglobin and transferrin variants, in a group of mothers of malformed newborns was investigated. In the first phase of the study, the results showed borderline statistical differences in the distribution of the transferrin types between the study group and a suitable control population. The second phase of the research, where only transferrin phenotypes were studied, showed the same trend as in the first one, but the results were not statistically significant. We conclude that probably there are no true distribution differences, but that it would be desirable to study this problem in a different ethnic group.     

Low birth weight and allergy: possible pleiotropic effect of ACP1

The well-known relationship between low birth weight and allergies prompted us to investigate a possible pleiotropic effect of ACP1 on these conditions. ACP1 is a polymorphic enzyme that affects signal transduction of insulin and other growth factors, T-cell receptor signaling, and the regulation of flavoenzyme activity. Our aim was to compare the relationship between ACP1 and allergy with the relationship between ACP1 and birth weight. We studied 299 subjects from the Caucasian population of England, 124 subjects from the Caucasian population of central Italy, and 302 healthy puerperae and their newborn babies from the same Caucasian populations. ACP1 phenotype was determined by starch gel electrophoresis on RBC hemolysate and by DNA analysis. Subjects with high ACP1 activity (ACP1 C,B phenotype) show a lower level of IgE compared to subjects with low ACP1 activity (p = 0.01). The proportion of infants with a birth weight below the first quartile is lower among infants born to mothers with high ACP1 activity than among infants born to mothers with medium-low activity (p = 0.01). The data suggest a protective effect of high-activity ACP1 C,B phenotype from low birth weight and from allergic manifestations after birth.     

ABO blood groups and fertility—with special reference to intrauterine selection due to materno-fetal incompatibility

The purpose of the present investigation was to study whether there is differential fertility between different mating types of ABO blood group system. Selective force which is operating through maternal-fetal incompatibility has been observed in the differential fertility between compatible and incompatible mating groups in the present sample of 183 families of Visakhapatnam town of Andhra Pradesh, India. The differences in the mean numbers of pregnancies as well as living children between the two major mating groups, compatible and incompatible are significant. The fertility rates of O fathers and O mothers were significantly higher than those in matings in which neither parents belongs to O. The selection is operating to reduce the gene ratio of A and to increase the gene ratios of O and B in this sample.     

Molecular genetic analysis of weak B blood group allele in Jinan population reveals distribution of ABw phenotype

The aim of this study was to investigate the distribution of the ABw phenotype of ABO blood group in the Jinan population. 31 856 samples were tested during the period 2018 to 2019. Thirty-nine samples with discrepant results, as identified by micro-column gel method, were further investigated by serological (tube technique) and molecular (fluorescence PCR, DNA sequencing) methods. Eight samples showed ABw phenotype, which accounted for 0.025% of the population tested. From the sequencing analysis, six samples (6/8) were typed as ABO*A1.02/ABO*BW.12 and two samples (2/8) as ABO*A1.02/ABO*BW.03. The study suggests that ABw12 account for 75% of ABw phenotype and indicate ABw12 is the main ABw phenotype in Jinan population.