Absence of red cell glutamic-pyruvate transaminase: discovery of a "silent" allele homozygote.

An individual with complete absence of red blood cell glutamic-pyruvate transaminase (GPT) activity has been discovered in a South African family of Lebanese origin. The subject, who also shows a low level of serum GPT, appears to be perfectly healthy. His children, all obligatory heterozygotes for the GPT0 allele, have lower than average levels of the red cell enzyme. An apparent instance of anomalous segregation of red cell GPT resulting from the inheritance of the GPT0 allele was recorded in one of the proband''s grandchildren.     

A 122.5-kilobase deletion of the P gene underlies the high prevalence of oculocutaneous albinism type 2 in the Navajo population

Oculocutaneous albinism (OCA) is a genetically heterogeneous disorder. There are four known types of OCA: OCA1-OCA4. The clinical manifestations of all types of OCA include skin and hair hypopigmentation and visual impairment. Although there are a few documented observations of high frequency of albinism among Native Americans, including the Hopi, Zuni, Kuna, Jemez, Laguna, San Juan, and Navajo, no causative molecular defect has been previously reported. In the present study, we show that albinism in one Native American population, the Navajo, is caused by a LINE-mediated 122.5-kilobase deletion of the P gene, thus demonstrating that albinism in this population is OCA2. This deletion appears to be Navajo specific, because this allele was not detected in 34 other individuals with albinism who listed other Native American origins, nor has it been reported in any other ethnic group. The molecular characterization of this deletion allele allowed us to design a three-primer polymerase chain reaction system to estimate the carrier frequency in the Navajo population by screening 134 unrelated normally pigmented Navajos. The carrier frequency was found to be approximately 4.5%. The estimated prevalence of OCA2 in Navajos is between approximately 1 per 1,500 and 1 per 2,000. We further estimate that this mutation originated 400-1,000 years ago from a single founder.     

Red cell glutamic-pyruvic transaminase polymorphism in a sample of the Italian population a new variant allele: GPT8.

247 individuals from Northern Italy have been tested for red cell glutamic-pyruvic transaminase (GPT) polymorphism. An abnormal phenotype has been detected. Family data support the hypothesis of the existence of a new variant allele, GPT8, at the GPT locus.     

Two previously undetected variants of glutamic-pyruvic transaminase found by acidic polyacrylamide gel electrophoresis.

Two new electrophoretic variants of glutamic-pyruvic transaminase (GPT) have been found by polyacrylamide gel electrophoresis at acidic pH. They appeared to represent a single allele, GPT 2, by the standard method of starch gel electrophoresis. Studies in families show that they are inherited as codominant alleles at the GPT locus. Population frequencies are about the same as those of other rare GPT variants. Their behavior on gels is consistent with both of them having substitutions of histidines in place of uncharged amino acids.     

Glutamate pyruvate transaminase null allele in seven new families

Summary Based upon aberrant segregation of glutamate pyruvate-transaminase (GPT) and reduced enzyme activity on electrophoresis, seven new families with a GPT null allele were identified during genetic linkage analysis for a number of different traits.Supported in part by grants MCH-927 and HD-04612 from the U.S. Public Health Service     

Population genetics of red cell enzymes in Pygmies: a conclusive account

In the course of a long-term research project, three groups of Pygmies and some non-Pygmy Central Africans have been examined for the following red cell enzyme markers: ACP, PGM1, PGM2, PEPA, PEPB, and PEPC, AK, ADA, and PHI. Several other red cell enzymes (ESD, CA1 and CA2, GPT, GLO, and DIA1) have been studied in only some of these groups. This paper reports all the information we obtained, including what we have already published. The following conclusions can be drawn from the whole body of data: (1) Gene patterns of Pygmies are those typical of other Africans (e.g.: lack of ADA2 and AK2 genes, low GPT2 gene frequency, polymorphism of the CA2 locus, and presence at polymorphic frequencies of PEPA2 allele. (2) Superimposed on this African genetic makeup, a number of Pygmy characters were identified, namely, a private polymorphism for the PGM26 Pygmy allele and possibly one for the PEPC2 allele, and particularly high ACPR and low PGM12 gene frequencies. (3) Some markers, especially PGM1 and ACP, turned out also to discriminate efficiently among different groups of Pygmies.     

Targeted ablation and reorganization of the principal preplate neurons and their neuroblasts identified by golli promoter transgene expression in the neocortex of mice

The present study delineates the cellular responses of dorsal pallium to targeted genetic ablation of the principal preplate neurons of the neocortex. Ganciclovir treatment during prenatal development (E11–E13; where E is embryonic day) of mice selectively killed cells with shared S-phase vulnerability and targeted expression of a GPT [golli promoter transgene, linked to HSV-TK (herpes simplex virus-thymidine kinase), τ-eGFP (τ-enhanced green fluorescent protein) and lacZ (lacZ galactosidase) reporters] localized in preplate neurons. Morphogenetic fates of attacked neurons and neuroblasts, and their successors, were assessed by multiple labelling in time-series comparisons between ablated (HSV-TK^+/0) and control (HSV-TK^0/0) littermates. During ablation generation, neocortical growth was suppressed, and compensatory reorganization of non-GPT ventricular zone progenitors of dorsal pallium produced replacements for killed GPT neuroblasts. Replacement and surviving GPT neuroblasts then produced replacements for killed GPT neurons. Near-normal restoration of their complement delayed the settlement of GPT neurons into the reconstituted preplate, which curtailed the outgrowth of pioneer corticofugal axons. Based on this evidence, we conclude that specific cell killing in ablated mice can eliminate a major fraction of GPT neurons, with insignificant bystander killing. Also, replacement GPT neurons in ablated mice originate exclusively by proliferation from intermediate progenitor GPT neuroblasts, whose complement is maintained by non-GPT progenitors for inductive regulation of the total complement of GPT neurons. Finally, GPT neurons in both normal and ablated mice meet all morphogenetic criteria, including the ‘outside-in’ vertical gradient of settlement, presently used to identify principal preplate neurons. In ablated mice, delayed organization of these neurons desynchronizes and isolates developing neocortex from the rest of the brain, and permanently impairs its connectivity.     

Whole-genome scan for guttural pouch tympany in Arabian and German warmblood horses

Equine guttural pouch tympany (GPT) is a hereditary disease in foals of several breeds, including thoroughbreds, Arabian, Quarter and warmblood horses. We performed a whole-genome scan for GPT in 143 horses from five Arabian and five German warmblood families and genotyped 257 microsatellites. Chromosome-wide significant linkage was detected on ECA2 and ECA15 using multipoint non-parametric linkage analyses. Analyses stratified by sex revealed chromosome-wide significant linkage on ECA2 for fillies and chromosome-wide significant linkage on ECA15 for colts. For Arabian colts, the quantitative trait locus (QTL) on ECA15 was genome-wide significant. Haplotypes including two to four microsatellites within the QTL on ECA2 and 15 in fillies and colts, respectively, were significantly associated with GPT for both breeds. Thus, our analysis indicated sex-specific QTL, a fact which is in agreement with a two- to fourfold higher incidence of GPT in females. This is the first report of QTL for equine GPT and a first step towards identifying genes responsible for GPT.     

Jesus, peyote, and the holy people: alcohol abuse and the ethos of power in Navajo healing

Of the three religious healing traditions that coexist within the contemporary Navajo health care system, the Native American Church (NAC) and Pentecostal Christianity are more actively involved in the treatment of alcohol and substance abuse than is Traditional Navajo healing. This article examines these two more recent healing traditions as religious responses to the contemporary Navajo crisis of alcohol and substance abuse as well as to socioeconomic changes. These traditions offer new kinds of power, social networks, and personal meaning that facilitate a transformation of self, a revitalized sense of community, and a new vision of the possibilities of the future for Navajo people who suffer. Examining the ethos of power that underlies Navajo healing can complement the theoretical emphasis on harmony and beauty in anthropological research on Navajo culture and religion.     

Navajo tribal mortality: A life table analysis of the leading causes of death

Abstract

The five leading causes of death for Navajo males and females are analyzed by life table methods. Navajo male and female life expectancy at birth were 58.8 and 71.8 years, respectively. The greatest increase in Navajo male life expectancy would result from the elimination of motor vehicle accidents (5.17 years at birth, and 3.11 years for working ages 15–65). The life expectancy of Navajo females would be lengthened the most (3.70 years) by elimination of circulatory system disease. For working‐ages gains for both sexes, however, the greatest benefit would result from elimination of motor vehicle accidents. The implications of the results are discussed in relation to the various public health programs and health planning efforts for the Navajo Nation.     

The whole universe is my cathedral: a contemporary Navajo spiritual synthesis

This article discusses the three major spiritual healing ways used by Navajo Indians today: Traditional healing practices that have been used for generations and still have a dynamic existence relevant to everyday Navajo life; Christian healing traditions, ranging from Catholic Charismatic to Protestant Pentecostal; and practices of the Native American Church (NAC). The complex relationship among these healing traditions on the Navajo reservation is examined through a case study of a Navajo woman whose personal spirituality includes all three. Faced with serious medical problems, this devout Catholic turned to Navajo Traditional and Native American Church spiritual diagnosis and treatment. This analysis is the occasion for a reflection on the contemporary relevance of the kind of spiritual synthesis characterized in this woman's experience.     

Depressive illness and Navajo healing

What is the experience of Navajo patients in Navajo religious healing who, by the criteria and in the vernacular of contemporary psychiatry, would be diagnosed with the disorder called depression? We ask this question in the context of a double dialogue between psychiatry and anthropology and between these disciplines' academic constructs of illness and those of contemporary Navajos. The dialogue is conducted in the arena of patient narratives, providing a means for observing and explicating processes of therapeutic change in individuals, for illustrating variations in forms of Navajo religious healing sought out by patients demonstrating similar symptoms of distress, and for considering the heuristic utility of psychiatric diagnoses and nomenclature in the conceptualization of illness, recovery, and religious healing. From among the 37 percent of patients participating in the Navajo Healing Project who had a lifetime history of a major depressive illness, three are discussed herein, their selection based on two criteria: (1) all met formal psychiatric diagnostic criteria for a major depressive episode at the time of their healing ceremonies, and (2) together, their experiences illustrate the range of contemporary Navajo religious healing, including Traditional, Native American Church (NAC), and Christian forms. We suggest that, despite the explicit role of the sacred in religious healing interventions available to Navajo patients, differences between biomedical and religious healing systems may be of less significance than their shared existential engagement of problems such as those glossed as depression.     

Human phylogenetic relationships according to the D1S80 locus

By analyzing the allelic frequencies at the D1S80 locus in 43 human populations, we show that the locus is polymorphic globally and that it can be used to discriminate between major racial groups and subpopulations through phylogenetic analysis. Although the use of informative multiple loci generally provides more accurate phylogenetic relationships, in instances where time and/or target DNA availability is limited, D1S80 could provide useful data to discriminate between human groups. Also, knowledge of which loci independently provide accurate phylogenetic relationships, such as the D1S80, can be used to design more accurate multi-locus combinations. In addition, allele frequencies at the locus are reported, for the first time, for Bahamian individuals of African origin and for Chimila, Bari, and Navajo (Cañoncito Valley) native Americans. Allelic data was obtained using standard polymerase chain reaction (PCR) techniques. In the four new populations, 65 genotypes and 20 segregating alleles were observed. All populations conformed to Hardy-Weinberg expectations except the Chimila.     

Associations of Circulating Oxidized LDL and Conventional Biomarkers of Cardiovascular Disease in a Cross-Sectional Study of the Navajo Population

The prevalences of cardiovascular disease (CVD) and type 2 diabetes (T2D) have increased among the Navajo Native American community in recent decades. Oxidized low-density lipoprotein (oxLDL) is a novel CVD biomarker that has never been assessed in the Navajo population. We examined the relationship of oxLDL to conventional CVD and T2D risk factors and biomarkers in a cross-sectional population of Navajo participants. This cross-sectional study included 252 participants from 20 Navajo communities from the Diné Network for Environmental Health Project. Plasma samples were tested for oxLDL levels by a sandwich enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used to determine the relationship of oxLDL and oxidized- to non-oxidized lipoprotein ratios to glycated hemoglobin (HbA1c), C-reactive protein (CRP), interleukin 6 (IL6) and demographic and health variables. Type 2 diabetes, hypertension and obesity are very prevalent in this Navajo population. HbA1c, CRP, body mass index (BMI), high-density lipoprotein, and triglycerides were at levels that may increase risk for CVD and T2D. Median oxLDL level was 47 (36.8–57) U/L. Correlational analysis showed that although oxLDL alone was not associated with HbA1c, oxLDL/HDL, oxLDL/LDL and CRP were significantly associated with HbA1c and glucose. OxLDL, oxLDL/HDL and oxLDL/LDL were significantly associated with CRP. Multivariate analysis showed that triglycerides were a common and strong predictor of oxLDL, oxLDL/HDL and oxLDL/LDL. OxLDL was trended with HbA1c and glucose but did not reach significance, however, HbA1c was an independent predictor of OxLDL/HDL. CRP trended with oxLDL/HDL and was a weak predictor of oxLDL/LDL. This Navajo subset appears to have oxLDL levels comparable to subjects without evidence of CVD reported in other studies. The high prevalence of T2D, hypertension and obesity along with abnormal levels of other biomarkers including HbA1c indicate that the Navajo population has a worsening CVD risk profile.     

Effect of different extenders on glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) release from frozen buffalo semen

Sixty buffalo semen samples (motility greater than 60%) were frozen in 3 extenders, viz., Tris yolk glycerol (TY-G), Citric acid whey glycerol (CAW-G) and Egg yolk glucose sodium bicarbonate glycerol (EYGSB-G) for studying the release of GOT and GPT enzymes in the extracellular fluid during pre-freezing (after first extension) and post-freezing (15 minutes and 30 days after freezing). Release of GOT and GPT enzymes was less in TY-G than CAW-G and EYGSB-G extenders. Significant differences (P<0.01) in GOT and GPT release were observed between extenders and bulls at various stages of freezing of semen.     

Cloning, sequence, and expression of a cDNA encoding hamster UDP-GlcNAc:dolichol phosphate N-acetylglucosamine-1-phosphate transferase

UDP-GlcNAc:dolichol phosphate N-acetylglucosamine-1-phosphate transferase (GPT) catalyzes the initial reaction required for synthesis of dolichol-P-P-oligosaccharides. We report here on the sequence and expression of a full-length cDNA clone encoding hamster GPT. The cDNA predicts a protein of 408 amino acid residues including 10 hydrophobic segments. Several portions of the hamster GPT sequence constituting one-third of the protein have 60% or greater identity with yeast GPT, and one-half of the conserved sequence falls within the hydrophobic segments. In addition, hamster GPT has two copies of a putative dolichol recognition sequence recently identified in three yeast enzymes that interact with dolichol. The protein lacks KDEL or DEKKMP-type carboxyl-terminal ER sorting sequences. When expressed in COS-1 cells, the cDNA causes a 5-7-fold increase of GPT activity in membrane fractions. The activity was completely inhibitable by tunicamycin, and the primary product was shown to be GlcNAc-pyrophosphoryldolichol. This cDNA represents the first enzyme of the dolichol-oligosaccharide biosynthetic pathway to be cloned from a vertebrate source and demonstrates structural homology between the enzymes of the yeast and mammalian pathways.     

A recessive deletion in the GlcNAc-1-phosphotransferase gene results in peri-implantation embryonic lethality.

Formation of the dolichol oligosaccharide precursor is essential for the production of asparagine- (N-) linked oligosaccharides (N-glycans) in eukaryotic cells. The first step in precursor biosynthesis requires the enzyme UDP-GlcNAc: dolichol phosphate N-acetylglucosamine-1-phosphate transferase (GPT). Without GPT activity, subsequent steps necessary in constructing the oligosaccharide precursor cannot occur. Inhibition of this biosynthetic step using tunicamycin, a GlcNAc analog, produces a deficiency in N-glycosylation in cell lines and embryonic lethality during preimplantation development in vitro, suggesting that N-glycan formation is essential in early embryogenesis. In exploring structure-function relationships among N-glycans, and since tunicamycin has various reported biochemical activities; we have generated a germline deletion in the mouse GPT gene. GPT mutant embryos were analyzed and the phenotypes obtained were compared with previous studies using tunicamycin. We find that embryos homozygous for a deletion in the GPT gene complete preimplantation development and also implant in the uterine epithelium, but die shortly thereafter between days 4-5 postfertilization with cell degeneration apparent among both embryonic and extraembryonic cell types. Of cells derived from these early embryos, neither trophoblast nor embryonic endodermal lineages are able to survive in culture in vitro. These results indicate that GPT function is essential in early embryogenesis and suggest that N-glycosylation is needed for the viability of cells comprising the peri-implantation stage embryo.     

Polymorphic biochemical systems in a population of newly arrived inhabitants of the northeastern USSR. IV. The characteristics of the genetic structure of persons with chronic pathological processes

Analysis of properties of the genetic structure in 2847 individuals with different chronic diseases (1261 men and 1586 women) for 14 polymorphic loci (AcP, PGM1, PGD, GPT, GLO-I, EsD, AK, Pp, E2, Hp, Gc, Tf, AB0 and Rh) is presented. Discrepancy between the observed and expected phenotype frequencies for PGM1, GLO-I, EsD and AB0 loci is observed in a sample of patients Deviation from the expected frequencies is unequal for the representatives of different sex. Male and female portions of the sample differ significantly from each other for AcP, GPT, GLO-I, AK, EsD, Tf and AB0 loci, i. e. for 7 from 14 systems analysed. Highly significant differences between healthy and sick individuals have been detected: in general samples for 8 loci (AcP, PGM1, GPT, GLO-I, AK, Pp, Hp, AB0); in men for 8 loci (AcP, GPT, AK, PGD, Pp, Tf, AB0); in women for 5 loci (PGD, Pp, Gc, Tf, AB0). The difference between sick and healthy individuals of different sex is not only of qualitative but also of quantitative expression. The difference between sick and healthy men is much stronger, as compared to that between women. A decline in the average heterozygosity is noted in sick individuals. From the results obtained it is possible to conclude that the group of different pathologic conditions for the complex of genetic parameters differs significantly from that of healthy individuals. This may be a reflection of adaptation and disadaptation processes under the extreme environmental conditions.     

Population structure of eastern Sicily

A sample of 465 persons from Eastern Sicily was studied for 11 red-cell enzymes, namely GLO, GPT, EsD, PGP, PGD, Dia, AcP, PGM, SOD, CAI and CAII. The allele frequencies were compared with those of other Italian populations and showed that the island is homogeneous with the mainland for these systems. The rate of heterozygosity was studied as a function of interparental distance; although high (0.77) the correlation did not reach significance.