Resume Au cours des quinze dernieres annees l'attention s'est beaucoup plus portee sur les enzymopathies hereditaires du globule rouge entrainant une anemie hemolytique que sur les deficits enzymatiques erythrocytaires non responsables d'une maladie hematologique. Dans cette derniere categorie, l'anomalie erythrocytaire constitue un indicateur precieux soit d'un deficit enzymatique generalise, soit de l'impact des modifications d'environnement sur le metabolisme intra-erythrocytaire. Le diagnostic de plusieurs enzymopathies sans retentissement hematologique peut etre aisement etabli par l'etude des globules rouges : c'est le cas de la galactosemie (deficit en galactose-1-phosphate uridyl transferase), du deficit en galactokinase, du deficit en hypoxanthine-guanine phosphoribosyltransferase et de l'acatalasemie. L'identification des heterozygotes est egalement possible. Pour la galactosemie, un depistage systematique a la naissance est realisable par l'etude d'un echantillon de sang seche sur papier filtre. Les anomalies nutritionnelles peuvent retentir sur l'equipement enzymatique erythrocytaire et conduire a un diagnostic errone d'enzymopathie hereditaire. L'exemple le plus frappant est celui du deficit en glutathion-reductase. Cette anomalie a longtemps ete consideree comme hereditaire. En fait, bien qu'une certaine variabilite genetique essentiellement decelable par electrophorese existe, la plupart des cas decrits correspondent a un deficit acquis, que l'on peut corriger in vitro par l'addition de FAD ou in vivo par l'administration de riboflavine. De meme l'activite de la transaminase glutamo-oxalo-acetique erythrocytaire depend de l'apport quotidien en pyridoxine. L'administration d'acide nicotinique multiplie par 10 le taux du NAD dans les globules rouges. Le bleu de methylene ou la diaminodiphenyl sulfone augmentent le glutathion erythrocytaire. La teneur en 2,3 diphosphoglycerate des globules rouges depend du taux d'hemoglobine et du pH sanguin. La connaissance et la comprehension de l'effet des variations de l'environnement sur les enzymes et le metabolisme erythrocytaires permettent d'envisager le traitement de certaines maladies metaboliques hereditaires. Nous avons essaye de traiter par l'acide nicotinique deux subets atteints d'anemie hemolytique congenitale ou spherocytaire due a un deficit en G6PD. Malgre l'absence de resultats positifs, il est permis d'esperer que sous une autre forme, une telle approche therapeutique puisse s'averer plus efficace.

Red cell metabolism

In most human populations, the ability to digest lactose contained in milk usually disappears in childhood, but in European-derived populations, lactase activity frequently persists into adulthood (Scrimshaw and Murray 1988). It has been suggested (Cavalli-Sforza 1973; Hollox et al. 2001; Enattah et al. 2002; Poulter et al. 2003) that a selective advantage based on additional nutrition from dairy explains these genetically determined population differences (Simoons 1970; Kretchmer 1971; Scrimshaw and Murray 1988; Enattah et al. 2002), but formal population-genetics–based evidence of selection has not yet been provided. To assess the population-genetics evidence for selection, we typed 101 single-nucleotide polymorphisms covering 3.2 Mb around the lactase gene. In northern European–derived populations, two alleles that are tightly associated with lactase persistence (Enattah et al. 2002) uniquely mark a common (∼77%) haplotype that extends largely undisrupted for >1 Mb. We provide two new lines of genetic evidence that this long, common haplotype arose rapidly due to recent selection: (1) by use of the traditional FST measure and a novel test based on pexcess, we demonstrate large frequency differences among populations for the persistence-associated markers and for flanking markers throughout the haplotype, and (2) we show that the haplotype is unusually long, given its high frequency—a hallmark of recent selection. We estimate that strong selection occurred within the past 5,000–10,000 years, consistent with an advantage to lactase persistence in the setting of dairy farming; the signals of selection we observe are among the strongest yet seen for any gene in the genome.

/pdf/genetic-signatures-of-strong-recent-positive-selection-at-2cnih38wg5.pdf

Genetic signatures of strong recent positive selection at the lactase gene.

https://www.cell.com/cell/pdf/S0092-8674(00)81646-3.pdf

Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome.

Psychological universals, or core mental attributes shared by humans everywhere, are a foundational postulate of psychology, yet explicit analysis of how to identify such universals is lacking. This article offers a conceptual and methodological framework to guide the investigation of genuine universals through empirical analysis of psychological patterns across cultures. Issues of cross-cultural generalizability of psychological processes and 3 cross-cultural research strategies to probe universals are considered. Four distinct levels of hierarchically organized universals are possible: From strongest to weakest claims for universality, they are accessibility universals, functional universals, existential universals, and nonuniversals. Finally, universals are examined in relation to the questions of levels of analysis, evolutionary explanations of psychological processes, and management of cross-cultural relations.

/pdf/psychological-universals-what-are-they-and-how-can-we-know-59stjcrgbs.pdf

Psychological universals: what are they and how can we know?

Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (213,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the 213,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia’s geographic space. Using data on 213,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the 213,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe.

/pdf/the-origins-of-lactase-persistence-in-europe-553ptfhim5.pdf

The Origins of Lactase Persistence in Europe

Lactose is a biologically unique sugar. In contrast to the other nutritionally important disaccharides, the α-glycosides maltose and sucrose, lactose is a β-glycoside. Lactose occurs in large amounts and as a free molecule only in milk. It is thus a biochemical and nutritional characteristic of mammals and is not present in other classes of animals. Sugars more common than lactose and more ancient in evolutionary terms would presumably suffice for the supply of energy to the young mammal. The development of the intricate mechanisms of lactase synthesis in the mammary gland and of lactose digestion in the intestinal tract would therefore run counter to evolutionary economy if lactose did not convey a special selective advantage during the suckling period. Evidence of such an advantage is not available at present. Adult mammals usually do not have access to milk in their natural environment, and their lactose digestion capacity declines after weaning. The human species is no general exception to this rule: in the majority of humans there is a gradual decline of lactase activity during early childhood. Adults with persistent lactase activity and correspondingly high lactose digestion capacity are common in only a few populations. The causes and distribution of this dimorphism of lactase activity in human adults will be the main subjects of this review.

Genetics of lactose digestion in humans

Lactose nutrition and natural selection.

The population of northern Thailand has one of the highest frequencies of alpha-thalassemia in the world. However, the available distributional data are controversial. In addition to deletional types of alpha-thalassemia Hb, type Constant Spring should also be taken into consideration in alpha-thalassemia population studies, because it causes clinical alpha-thalassemia in the homozygous state or when present with both alpha-globin genes deleted in trans. We have examined a sample of 215 healthy subjects from four rural districts of Chiang Mai province. Out of these, 77 exhibited anomalies of the alpha-globin genes (alpha alpha/-alpha 3.7 in 36; -alpha 3.7/-alpha 3.7 in 3; -SEA in 30; alpha alpha/alpha CS alpha in 5; alpha alpha alpha anti 3.7 in 3). Therefore, no fewer than 2% of the children in northern Thailand are expected to be born with HbH disease or thalassemic hydrops fetalis. The considerable public health problem of hemoglobinopaties and the increasing acceptance of family planning necessitates facilities for the pre- and postnatal diagnosis of these disorders at the DNA level.

Prevalence of α-thalassemias in northern Thailand

HÆMOGLOBIN TAK: A VARIANT WITH ADDITIONAL RESIDUES AT THE END OF THE β-CHAINS

In Southeast Asia there seems to exist a relationship between Austroasiatic (Mon-Khmer) linguistic affiliation and a high prevalence of haemoglobin E. This hypothesis was tested in Assam, the north-eastern state of India, by examining three population groups: (1) Assamese, (2) Ahom, a Thai group related to the Shan in Burma, and (3) Khasi, a matrilineal Austroasiatic group. There were no differences in the frequency of ABO blood groups and G-6-PD deficiency between the three groups. The frequency of the haemoglobin E gene differed significantly, and there was a reciprocal relationship between the frequencies of the haemoglobin E and the β-thalassaemia genes.

Gebhard Flatz

Papers

Genetics of lactose digestion in humans

Lactose nutrition and natural selection.

Prevalence of α-thalassemias in northern Thailand

HÆMOGLOBIN TAK: A VARIANT WITH ADDITIONAL RESIDUES AT THE END OF THE β-CHAINS

Genetic survey in the population of Assam. I. ABO blood groups, glucose-6-phosphate dehydrogenase and haemoglobin type.