Population affinities of Neolithic Siberians: a snapshot from prehistoric Lake Baikal.

Archaeological evidence supports the inhabitation of the Lake Baikal region since the Paleolithic. Both metric and nonmetric osteological studies suggest that Neolithic Cis-Baikal populations are the ancestors of contemporary inhabitants of the region. To date, ancient DNA data have not been used to corroborate this biological continuity hypothesis. This study presents a temporal snapshot of the Cis-Baikal Neolithic by examining mtDNA diversity in two cemetery populations situated on the Angara River downstream of Lake Baikal. The 800 years separating the use of the two cemeteries is thought to represent a biocultural hiatus in the Cis-Baikal region, one that ended when a new group migrated into the area. To assess the likelihood that genetic continuity exists between these two Neolithic groups, we examined both mtDNA coding region and hypervariable region I (HVI) polymorphisms from skeletal remains excavated from both cemeteries (Lokomotiv and Ust'-Ida). The mtDNA haplogroup distributions of the two cemetery populations differ significantly, suggesting that they were biologically distinct groups. When the biological distance between these Neolithic groups is compared with modern Siberian and other East Eurasian groups, the posthiatus group (Serovo-Glazkovo) generally aligns with contemporary Siberians, while the prehiatus (Kitoi) individuals are significantly different from all but modern Kets and Shorians living in the Yenisey and Ob River basins to the west of Lake Baikal. These results suggest that the Lake Baikal region experienced a significant depopulation event during the sixth millennium BP, and was reoccupied by a new immigrant population some 800 years later.

Laboratory screening for genetic disorders and birth defects.

Screening for inherited disease is a preventative health measure that started in the 1960s with the development of programs for the detection of PKU in newborns and that has had a major impact on reducing the burden of disease. Developments in technology have led to the availability of large scale testing for an increasing number of both acquired and genetic disorders. Laboratory testing is only one facet of a screening program and consideration should be given to availability of testing to all individuals, education regarding the program, effectiveness of treatment, long-term benefits both for individuals and society, ethical issues, and cost benefits. In this review, newborn, prenatal, and heterozygote screening are discussed.

Mirror-image dental fusion and discordance in monozygotic twins.

A pair of monozygotic twins had similar but not identical dental anomalies. One twin had fusion of deciduous mandibular lateral incisor and canine on the left, with normal dentition on the right; the co-twin had right mandibular incisor/canine fusion, with aplasia of the lateral incisor on the left. These findings are discussed in the context of the related phenomena of situs inversus, mirror-imaging in twins, and gradients of severity of anomalies in the four copies of the mandibular developmental dental field.

Biochemical investigation of a child with molybdenum cofactor deficiency.

A girl aged eight months, who presented with developmental delay and dislocated optic lenses, was diagnosed as having combined sulfite oxidase and xanthine dehydrogenase deficiencies consistent with molybdenum cofactor deficiency. The diagnosis was confirmed by demonstrating the absence in urine of urothione, a molybdenum cofactor metabolite. Prenatal diagnosis excluded the disease in the mother's second pregnancy. A summary of an in vitro study of molybdenum cofactor synthesis in the patient is given.

Molecular characterisation of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null(Newport) (Gly115----Ser) and (Pi) Z Wrexham (Ser-19----Leu).

Two single point mutations in the alpha-1-antitrypsin gene, resulting in AAT deficiency, have been characterised in heterozygotes by DNA amplification and direct sequencing. The mutations result in amino acid substitutions, Gly115----Ser and Ser-19----Leu, in the leader sequence, respectively, and have been designated Pi Null(Newport) and Pi Z Wrexham. In the two families studied the mutations occur on chromosomes which also carry the common mutation causing Z deficiency. Individuals with such a deficiency are, therefore, compound heterozygotes. It is not known if these particular mutations would only cause a mild form of AAT deficiency in the absence of the Z mutation as they do not appear to cause predictable folding abnormalities. They do, however, result in severe deficiency when the Z mutation occurs in the same gene.

Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) nullcardiff (Asp256----Val); PiMmalton (Phe51----deletion) and PiI (Arg39----Cys).

Three mutations causing alpha-1-antitrypsin deficiency have been identified by gene amplification and direct DNA sequencing. In the Pi (proteinase-inhibitor) nullcardiff gene, the codon for aspartate at position 256 has mutated to encode valine. In PiMmalton and Pi I, the respective mutations are the deletion of the codon for a phenylalanine residue at position 51 or 52, and a single base substitution resulting in arginine being replaced by cysteine at position 39. Examination of the protein tertiary structure suggests that all of these mutations are likely to result in folding abnormalities that may explain the deficiency states.

Alpha 1 antitrypsin deficiency due to Pi null: clinical presentation and evidence for molecular heterogeneity.

The proteinase inhibitor null (Pi-) allele is a rare cause of alpha 1 antitrypsin (AAT) deficiency. In three families, all the subjects with AAT deficiency due to PiZ- presented in early childhood with recurrent chest infections and wheezing presumably related to passive smoking. In Pi- the AAT gene is present and there is no evidence for a gene deletion. In one family a restriction fragment length polymorphism (RFLP) detected with the enzyme XbaI segregates with the Pi- allele. In a family where a consanguineous marriage occurred, the XbaI polymorphism segregates with the normal M1 allele rather than Pi-, suggesting that Pi- may have originated from M1. In contrast, a third family and 20 normal unrelated subjects do not show the RFLP.

Serum free thyroxine and free triiodothyronine concentrations in healthy fullterm, preterm and sick preterm neonates.

There are few data available on free thyroid hormone concentrations in the early neonatal period. With the widespread application of screening procedures for detecting congenital hypothyroidism there is a need for reference ranges in neonates. In this study we have evaluated thyroid function in healthy fullterm and preterm neonates, and sick neonates all within one to 10 days postnatal age. Our data indicates that free thyroxine but not free triiodothyronine is higher in fullterm neonates than the adult reference range and that both free thyroid hormone concentrations are reduced in healthy and sick preterm neonates as compared to fullterm neonates. Assessment of thyroid function in the early neonatal period needs to take into account these changes particularly in preterm and sick preterm neonates.

Normal reference ranges for biochemical substances relating to renal, hepatic, and bone function in fetal and maternal plasma throughout pregnancy.

Normal reference ranges for sodium, potassium, urea, creatinine, calcium, phosphate, total protein, albumin, bilirubin, alkaline phosphatase, and aspartate transaminase were determined from 344 fetal and maternal plasma samples between 15 and 38 weeks' gestation. Pure fetal blood was obtained by fetoscopy in the second trimester and in the third trimester by umbilical cord puncture at delivery. All biochemical substances were measured by continuous flow (SMAC, Technicon) except albumin, which was measured by turbidimetry (CobasBio, Roche). The resulting data were analysed on an AMDAHL 470A computer and reference ranges covering 2.5 to 97.5 percentiles were defined. Analysis of variance was performed to examine the overall effect of gestational age on the analytes measured and on the changes in the fetal compartment relative to the mothers'. A paired t test was performed to examine how these biochemical substances in fetal plasma related to maternal plasma from the same pregnancy.