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Suicide and attempted suicide in Greenland. A controlled study in Nuuk (Godthaab).

Suicidal behaviour in Eskimo populations has changed in pattern and quantity over the last decades. Rates have more than quadrupled and performers now are mainly young persons with obscure motivation. In a study from Greenland's major township all cases of attempted or completed suicide among Greenlanders are analysed for social, emotional, somatic, and environmental predisposing factors in comparison with a non-psychiatric, never-suicidal, matching group. Almost two per thousand of the adult population committed suicide yearly while attempts at suicide were five times as frequent. A quarrelsome, drinking, childhood home background was often found, at least as regards the attempters, who themselves frequently suffered from emotional conflicts with close contacts, alcohol affliction, criminality, and instability at work. Neither bereavement, cross-cultural exposure, broken homes, nor meteorological factors seemed to exert a significant influence. The results are discussed in relation to the social and cultural evolution of the Greenlandic society.

Adult↗

Genetics of choroid plexus tumors.

Choroid plexus tumors consist of papillomas and carcinomas. A variety of germline and somatic genetic changes have been demonstrated for each of these subtypes. In this paper, the authors summarize the current knowledge of the genetic bases of these tumors.

Cerebral Ventricle Neoplasms↗

Analysis of (CAG)n size heterogeneity in somatic and sperm cell DNA from intermediate and expanded Huntington disease gene carriers.

The length of the CAG repeat responsible for Huntington disease has been analysed by two PCR methods in blood and sperm DNA of 13 expansion carriers, two carriers of intermediate alleles, and four normal subjects. The two methods consistently confirmed size heterogeneity, more pronounced in sperm and confined to the CAG stretch. Based on densitometric scanning of films, four indexes addressed to different features of the PCR pattern were used to quantitate mosaicism. These revealed strong correlations with CAG size and intergenerational instability. However, mosaicism did not show a greater similarity in sibs who shared the same HD chromosome, nor was correlated with instability in the proband's pedigree. Our data do not support the hypothesis that cis-acting factors play a major role in the instability and leave the CAG size per se as the major determinant of sperm cell CAG instability.

Adolescent↗

Molecular characterization of pancreatic serous microcystic adenomas: evidence for a tumor suppressor gene on chromosome 10q.

Pancreatic serous microcystic adenomas (SCAs) are rare, benign tumors with a striking female preference. Virtually no information is available about chromosomal or genetic anomalies in this disease. We performed extensive molecular characterization of 21 cases of formalin-fixed, paraffin-embedded sporadic SCAs consisting in genome-wide allelic loss analysis with 79 microsatellite markers covering all 22 autosomes, assessment of microsatellite instability, and mutational analysis of the VHL, K-ras, and p53 genes in nine cases for which frozen tissue was available. Although no case showed microsatellite instability of the type seen in mismatch repair-deficient tumors, a relatively low fractional allelic loss of 0.08 was found. Losses on chromosome 10q were the most frequent event in SCAs (50% of cases), followed by allelic losses on chromosome 3p (40% of cases). Moderately frequent losses (>25% of cases) were found on chromosomes 1q, 2q, and 7q. The VHL gene, located on chromosome 3p, had somatic inactivating mutations in two of nine cases (22%), whereas no mutations were found in either K-ras or p53, in agreement with the finding that all 21 cases stained negative for p53 by immunohistochemistry. Our study indicates that the involvement of chromosomal arms 10q and 3p is characteristic of SCAs and that the VHL gene is involved in a subset of sporadic cases.

Aged↗

Spontaneous and synaptic excitation of paramedian reticular neurones in the decerebrate cat.

1. In decerebrate cats neurones in the region of the paramedian reticular nucleus were identified by responses to stimulation of implanted cerebellar electrodes. Approximately one half were antidromically activated and one half orthodromically. 2. Somatic stimulation and electrical stimulation of both hind limb and cranial nerves activated many of these cells. There was no correlation between the effects of these stimuli on cell firing and on blood pressure. 3. A number of rhythms in spontaneous firing were observed. One fifth of cells fired with the rhythm of efferent activity in the recurrent laryngeal nerve. In animals showing cycles of stability and instability in blood pressure corresponding phases of activity and inactivity in the firing of paramedian reticular neurones were observed. 4. Most paramedian reticular cells showed bursts of firing preceding abrupt rises in blood pressure but this was also observed with cells lateral to this area. 5. One third of cells studied showed changes in firing rate correlated with the changes in blood pressure which followed I.V. acetylcholine and noradrenaline. 6. Bilateral carotid artery occlusion, which always produced a rise in blood pressure, had little effect on cell firing.

Abdomen↗

Does human sperm nuclear DNA integrity affect embryo quality?

Abnormalities in the male genome are a clear potential reason for post fertilization failure. Male infertility may arise due to high levels of loosely packaged chromatin and damaged DNA. The achievement of a correct chromatin packaging level is essential for successful fertilization. The chromatin contained in the nuclei of mammalian spermatozoa is an extremely compact and stable structure. The reports on mammalian spermatozoa indicate that available volume is insufficient to contain sperm chromatin packed in nucleosome like structure and thus is organized in a special way. Different unique properties of sperm DNA like high degree of inertness and stability, absence of transcription, replacement of somatic histone by protamine etc have made the study of sperm chromatin more interesting. Increased levels of sperm nuclear DNA damage exist in infertile men with abnormal sperm parameters (i.e. concentration, motility and morphology), and various assay techniques have been developed to evaluate sperm chromatin maturity/DNA integrity. These assays are based on the facts that defects in chromatin structure have been shown to lead to increased DNA instability and sensitivity to denaturing stress. DNA integrity in the sperm is essential for the accurate and successful transmission of genetic information. Importance of sperm DNA has also become more obvious in the context of assisted reproductive techniques. While recent advances in assisted reproductive technologies have made possible and practical for many infertile men to become father, the risk of transmission of genetic mutation to the offspring, however, still remains. Further research is necessary to devise techniques for identification and selection of sperm with undamaged DNA for ICSI or to remove sperm with damaged DNA from the semen sample to improve the pregnancy outcome in ICSI.

Animals↗

Causes and consequences of microsatellite instability in endometrial carcinoma.

Genetic instability of microsatellite repeat sequences [microsatellite instability (MI)] is commonly seen in tumors associated with the hereditary nonpolyposis colorectal cancer syndrome and is a result of inactivating mutations in any of several genes involved in a particular pathway of DNA mismatch repair. Sporadic (i.e., nonhereditary) manifestations of several tumor types, including colorectal, gastric, and endometrial carcinomas, also exhibit MI in a significant fraction of cases. Many MI+ sporadic colorectal carcinomas are associated with somatic mutations of mismatch repair genes, and several genes with coding region microsatellites are frequently mutated as a result in these cancers. The molecular causes and consequences of MI in sporadic endometrial carcinomas remain obscure, however. The aims of this study were: (a) to identify a series of sporadic endometrial carcinomas with clear evidence of MI; (b) to determine the extent to which somatic alterations in mismatch repair genes are associated with this MI; and (c) to establish whether the genes containing coding region microsatellite repeats that are known to be disrupted in MI+ gastrointestinal cancers are also disrupted in MI+ endometrial carcinomas. Matched pairs of normal and tumor DNA from 57 consecutive cases of endometrial carcinoma were examined for evidence of MI using a consensus panel of microsatellite markers. Fourteen cases (25%) displayed unequivocal evidence of MI, consistent with previously published estimates of the incidence of MI+ sporadic endometrial carcinoma. These cases were subjected to a mutation screen of the coding regions and exon-intron boundaries of the mismatch repair genes MSH2 and MLH1. Although several polymorphisms were detected, no clearly deleterious mutations were found in either of these genes. Notably, however, hypermethylation of the MLH1 promoter region was identified in 10 of 14 (71%) MI+ cases. Somatic mutations in coding region microsatellite repeats in the TGFbetaIIR, IGFIIR, BAX, E2F4, MSH3, MSH6, BRCA1, and BRCA2 genes were generally rare. Four MI+ tumors (29%) contained somatic mutations in the PTEN gene, only one of which was likely the result of MI. These data indicate that somatic mutational inactivation of known mismatch repair genes does not account for the great majority of sporadic endometrial carcinomas with MI and that a significant fraction of these cases may instead be causally associated with hypermethylation of the MLH1 promoter. Furthermore, genes with coding region microsatellites that are frequently mutated in MI+ gastrointestinal cancers are rarely mutated in MI+ endometrial cancers, implying the existence of alternative molecular targets for the tumorigenic effects of MI in this tumor type.

Adaptor Proteins, Signal Transducing↗

Analysis of genomic instability using multiple assays in a patient with Rothmund-Thomson syndrome.

We report on a patient with Rothmund-Thomson syndrome (RTS) whose cytogenetic evaluation showed a normal karyotype with no evidence of trisomy mosaicism or chromosomal rearrangements. Cultured lymphocytes from the patient, her mother, and a control exposed to mitomycin C and diepoxybutane did not show increased sensitivity to the dialkylating agents. Unlike some previous reports, we found no evidence of a deficiency in nucleotide excision repair, as measured with the functional unscheduled DNA synthesis assay. Glycophorin A analysis of red blood cells for somatic mutation revealed suspiciously high frequencies of both allele loss and loss-and-duplication variants in the blood of the patient, a pattern consistent with observations in other RecQ-related human diseases, and evidence for clonal expansion of a mutant clone in the mother. Discrepant results in the literature may reflect true heterogeneity in the disease or the fact that a consistent set of tests has not been applied to RTS patients.

Adult↗

Recovery of a marked translocation strain that will facilitate the isolation of balancer chromosomes in the Mediterranean fruit fly, Ceratitis capitata.

The results of two screens for mutations and chromosomal aberrations in Ceratitis capitata are presented. Three dominant mutations were recovered, including Sb, which is associated with a homozygous lethal translocation between the third and fifth chromosomes, T(3;5)Sb, with the fifth chromosome breakpoint adjacent to y. The T(3;5)Sb chromosome is maintained by selecting for Sb in a T(3;5)Sb, w2 Sb y2 wp/w2 y2 wp stock and can be used to distinguish between other chromosomes carrying differential combinations of the recessive markers w2 y2 wp. The ability to isolate particular marked chromosomes is essential in order to recover an inversion-based balancer chromosome. In addition to the recovery of dominant mutations, gamma-ray induced somatic mosaics of w2 and y2 and zygotic w mosaics were found. The generation of zygotic mosaics following mutagenesis can give mutants with a mosaic germ line that fail to breed true in the first generation. A screen of 22,830 irradiated chromosomes failed to recover variegating alleles of w, although such alleles might be recovered in a larger screen. The high frequency of dominant mutations and the instability at the w locus in our stocks implies a background level of dysgenic activity. These results have implications for the construction and long-term maintenance of genetically modified strains.

Alleles↗

Genomic instability in 1p and human malignancies.

Both cytogenetic and molecular genetic approaches have unveiled non-random genomic alterations in 1p associated with a number of human malignancies. These have been interpreted to suggest the existence of cancer-related genes in 1p. Earlier studies had employed chromosome analysis or used molecular probes mapped by in situ hybridization. Further, studies of the various tumor types often involved different molecular probes that had been mapped by different technical approaches, like linkage analysis, radioactive or fluorescence in situ hybridization, or by employing a panel of mouse x human radiation reduced somatic cell hybrids. The lack of maps fully integrating all loci has complicated the generation of a comparative and coherent picture of 1p damage in human malignancies even among different studies on the same tumor type. Only recently has the availability of genetically mapped, highly polymorphic loci at (CA)n repeats with sufficient linear density made it possible to scan genomic regions in different types of tumors readily by polymerase chain reaction (PCR) with a standard set of molecular probes. This paper aims at presenting an up-to-date picture of the association of 1p alterations with different human cancers and compiles the corresponding literature. From this it will emerge that the pattern of alterations in individual tumor types can be complex and that a stringent molecular and functional definition of the role that Ip alterations might have in tumorigenesis will require a more detailed analysis of the genomic regions involved.

Chromosome Mapping↗

Microsatellite instability and mutation analysis of candidate genes in unselected sardinian patients with endometrial carcinoma.

BACKGROUND: Microsatellite instability (MSI) is due mostly to a defective DNA mismatch repair (MMR). Inactivation of the two principal MMR genes, hMLH1 and hMSH2, and the PTEN tumor suppressor gene seems to be involved in endometrial tumorigenesis. In this study, Sardinian patients with endometrial carcinoma (EC) were analyzed to assess the prevalence of both the mutator phenotype (as defined by the presence of MSI and abnormal MMR gene expression at the somatic level) and the hMLH1, hMSH2, and PTEN germline mutations among patients with MSI positive EC. METHODS: Paraffin embedded tissue samples from 116 consecutive patients with EC were screened for MSI by polymerase chain reaction-based microsatellite analysis. Immunohistochemistry (IHC) with anti-hMLH1 and anti-hMSH2 antibodies was performed on MSI positive tumor tissue sections. Germline DNA was used for mutational screening by denaturing high-performance liquid chromatography analysis and automated sequencing. RESULTS: Thirty-nine patients with EC (34%) exhibited MSI; among them, 25 tumor samples (64%) showed negative immunostaining for hMLH1/hMSH2 proteins (referred to as IHC negative). No disease-causing mutation within the coding sequences of the hMLH1/hMSH2 and PTEN genes was found in patients with EC who had the mutator phenotype (MSI positive and IHC negative), except for a newly described hMLH1 missense mutation, Ile655Val, that was observed in 1 of 27 patients (4%). Although MSI was more common among patients with advanced-stage EC and increased as the tumor grade increased, no significant correlation with disease free survival or overall survival was observed among the two groups (MSI positive or MSI negative) of patients with EC. CONCLUSIONS: In patients with MSI positive EC, epigenetic inactivations rather than genetic mutations of the MMR genes seem to be involved in endometrial tumorigenesis. No prognostic value was demonstrated for MSI in patients with EC.

Adaptor Proteins, Signal Transducing↗

Mutation rate heterogeneity and the generation of allele diversity at the human minisatellite MS205 (D16S309).

Many tandemly repeated minisatellite loci display extreme levels of length variation as a consequence of high rates of spontaneous germline mutation altering repeat copy number. Direct screening for new allele lengths by small-pool PCR has shown that instability at the human minisatellite locus MS205 (D16S309) is largely germline specific and usually results in the gain or loss of just a few repeat units. Structural analysis of the order of variant repeats has shown that these events occur preferentially at one end of the tandem array and can result in complex rearrangements including the inter-allelic transfer of repeat units. In contrast, putative mutants recovered from somatic DNA occur at a substantially lower rate and are simple and non-polar in nature. Germline mutation rates vary considerably between alleles, consistent with regulation occurring in cis. Although examination of DNA sequence polymorphisms immediately flanking the minisatellite reveals no definitive associations with germline mutation rate variation, differences in rate may be paralleled by changes in mutation spectrum. These findings help to explain the diversity of MS205 allele structures in modern humans and suggest a common mutation pathway with some other minisatellites.

Alleles↗

Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genes.

To date, at least four genes involved in DNA mismatch repair (MMR) have been demonstrated to be altered in the germline of patients with hereditary nonpolyposis colon cancer: hMSH2, hMLH1, hPMS1, and hPMS2. Additionally, loss of MMR function has been demonstrated to lead to the phenomenon of microsatellite instability (MIN) in tumors from these patients. In this study, we have examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in paraffin-embedded tumors from 7 patients with MIN+ sporadic cancer, 13 patients with familial colorectal cancer, and 12 patients meeting the strict Amsterdam criteria for hereditary nonpolyposis colon cancer. The relationship between the expression of these two gene products, the presence of germline or somatic mutations, and the presence of tumor MIN was examined. Nineteen of the 28 tumors studied demonstrated MIN, whereas mutations in hMLH1 and hMSH2 were detected in 6 and 2 patients, respectively. Of the eight MIN+/mutation+ cases, the absence of protein expression was observed for the corresponding gene product in all but one case (missense mutation in hMLH1). However, seven MIN+/mutation- cases also showed no expression of either hMLH1 (n = 5), hMSH2 (n = 1), or both (n = 1), whereas four MIN+/mutation- cases demonstrated normal expression for both. None of the MIN-/mutation- cases (n = 9) demonstrated an altered expression pattern for either protein. These data suggest that examination of protein expression by immunohistochemistry may be a rapid method for prescreening tumors for mutations in the MMR genes.

Adaptor Proteins, Signal Transducing↗

Mitochondrial microsatellite instability of colorectal cancer stroma.

Mitochondrial microsatellite instability (mtMSI) and mutations of mitochondrial DNA has been reported in cancer epithelia of carcinomas. However, mtMSI in cancer stroma has not yet been identified in human cancers. In this study, we attempted to determine if mtMSI occurs in the cancer stroma of sporadic colorectal cancers, and if the stromal mtMSI has any correlations with stromal nuclear MSI (nMSI) and cancer epithelial mtMSI. Nine microsatellite sequences within the D-loop and 5 coding genes for mtMSI, and 9 microsatellites for nMSI were analyzed in the microdissected cancer epithelia and adjacent stromas of 48 sporadic colorectal cancers. Overall, 23 somatic mitochondrial DNA alterations were detected in 15 cancer epithelia (31.2%) and 5 stromas (10.4%). The mutations consisted of 19 D-loop mtMSI alterations, and 1 missense and 3 framshift mutations of repeat sequences within the coding genes. All of the 5 stromal genetic alterations showed D-loop mtMSI. In regards to other MSI status, the stromal mtMSI had no association with stromal nMSI or epithelial mtMSI, either. These findings indicate that in addition to the cancer epithelia the cancer stroma harbor mtMSI, and suggest a possible role of stromal mtMSI in the pathogenesis of colorectal cancers. Furthermore, the data suggest that stromal mtMSI may occur independently of stromal nMSI and epithelial mtMSI in sporadic colorectal cancers.

Chromosome Mapping↗

Prognosis in DNA mismatch repair deficient colorectal cancer: are all MSI tumours equivalent?

Microsatellite instability (MSI) in colorectal tumours is the hallmark of defective DNA mismatch repair (MMR) and high level MSI can be detected in up to 15% of incident colorectal cancers. MSI in sporadic colorectal tumours is primarily due to epigenetic silencing of MLH1 while MSI is almost universal in tumours from HNPCC family members due to germline MMR gene mutation with loss or mutational inactivation of the second copy as a somatic event. There is evidence that tumour MSI is associated with a better outcome than the generality of large bowel malignancy. However, although MSI occurs in both sporadic colorectal cancer and in tumours arising in patients with germline MMR gene mutations, cancer survival should not be considered to be equivalent for these two groups with MSI tumours simply because both exhibit similarities in molecular phenotype. Here, we review the evidence on prognosis in patients with sporadic MSI tumours compared to those who have inherited a germline DNA MMR repair gene defect. In addition, we explore whether there are variables that afford opportunity to distinguish three groups on the basis of MSI status, namely: sporadic MSI tumours; MSI tumours in carriers of germline MMR gene defects; microsatellite stable (MSS) tumours. Differences in prognosis between these three groups is important because it underpins the rationale for surveillance and early identification of tumours in MMR gene carriers, as well as refining understanding of the influence of MSI on cancer progression. Furthermore, we discuss the effect of MSI on the effectiveness of chemotherapy regimens.

Base Pair Mismatch↗

Attempts to detect retrotransposition and de novo deletion of Alus and other dispersed repeats at specific loci in the human genome.

Dispersed repeat elements contribute to genome instability by de novo insertion and unequal recombination between repeats. To study the dynamics of these processes, we have developed single DNA molecule approaches to detect de novo insertions at a single locus and Alu-mediated deletions at two different loci in human genomic DNA. Validation experiments showed these approaches could detect insertions and deletions at frequencies below 10(-6) per cell. However, bulk analysis of germline (sperm) and somatic DNA showed no evidence for genuine mutant molecules, placing an upper limit of insertion and deletion rates of 2 x 10(-7) and 3 x 10(-7), respectively, in the individuals tested. Such re-arrangements at these loci therefore occur at a rate lower than that detectable by the most sensitive methods currently available.

Alu Elements↗

[Post-traumatic stress disorder (PTSD): the syndrome with multiple faces].

We choose to discuss from the PTSD's point of view because this diagnostic reference is commonly used. We wish outline its restrictive sight which could prevent the professional from having a diagnosis of PTSD. We don't want to say there is a PTSD everywhere but it appears to us that a traumatic reading can be a precious advantage for the clinician to establish a real therapeutic relation with some patients. Post-traumatic syndrome differs from the majority of other diagnostic categories as it includes in its criteria the presumptive cause of the trauma (criterion A). In the case that this syndrome originates in war experiences, the presumed cause presents itself as an exceptional event overcoming the individual's resources. The notion of war traumatisation has been extended to other events such as catastrophes, physical attacks, rapes, child and wife battering, and sexual abuses. But the events which cause PTSD (Post-Traumatic Stress Disorder) are significantly more numerous. It can be seen that medical events such as giving birth, miscarriage, heart attack, cancer, or hospitalisation following resuscitation may give rise to PTSD. Further, people experiencing prolonged periods of distress may equally develop a post-traumatic syndrome without any particular event having occurred to surpass their defences. It's the case of the Prolonged Duress Stress Disorder (PDSD). The series of discontinuous stress "waste" the psychic balance and may give rise, at one moment, to posttraumatic symptoms described in DSM, without any specific stressful event. The existence of criterion A is therefore not a necessary prerequisite in establishing a diagnosis of PTSD. It is, in fact, very difficult to predict which events could cause a PTSD, and this, especially, as the subjective aspects count at least as much as the objective aspects. The clinician should have to carefully explore how the patient experienced the event or, how he apprehended the event itself and it's outcome, if he wants get the traumatic range of a life event. The feeling of deep distress, the feeling of being trapped, the loss of control, the collapse of basic beliefs, the feeling that one's life is in jeopardy, that the physical integrity is (really or in one's imagination) threatened, the feeling of helplessness, are quite as much clues for a possible PTSD which hides behind others clinical manifestations either psychological or somatic. Furthermore, the "pure" form described in the DSM and grouping together three further criteria (reliving events, avoiding stimuli associated with the trauma, hyper-reactivity) is extremely rare in the chronic form. An untreated post-traumatic syndrome evolves with time and may present, initially, with very different pathological symptoms giving rise to equally varied diagnoses. Different etiopathogenic models propose to account for the PTSD 's heterogeneous appearance and instability with time. The comorbidity concept sees the PTSD as an independent entity other independent pathologies coexist with. The typologic concept suggests that the PTSD is an independent entity which shows different clinical appearances based on symptomatic descriptions. The "cascade" concept suggests to see the PTSD as an independent entity which offers, with time, different symptomatic appearances, in evolution, because of events caused by after effects, in different areas of the PTSD itself. All of these concepts outline the transnosologic appearance of the PTSD which makes it hardly recognizable. The "chronic" syndrome is rarely diagnosed forming a real challenge to prevention. In effect, the present authors insist on the crucial nature of early detection of PTSD since the greater the time elapsed the more difficult it becomes due to the evolutionary aspect of the syndrome, which initially has more readily recognizable symptoms. The consequences of an unrecognised PTSD are serious and affect both the individual and his immediate family and friends, contributing further to the aggravation of the problems. When a PTSD is diagnosed, it can allow the clinician to further a more global care which will help the patient to get a better recovery. With patients who suffered an infarct, the treatment of PTSD which prevents their recovery will help to go back to the way they lived before the event. It has been showed how important could be the PTSD detection on the severe burned people's pain control. Thus it seems to be crucial for the clinician to keep this diagnosis in mind alongside any other.

Adolescent↗

Processes of copy-number change in human DNA: the dynamics of {alpha}-globin gene deletion.

Ectopic recombination between locally repeated DNA sequences is of fundamental importance in the evolution of gene families, generating copy-number variation in human DNA and often leading to pathological rearrangements. Despite its importance, little is known about the dynamics and processes of these unequal crossovers and the degree to which meiotic recombination plays a role in instability. We address this issue by using as a highly informative system the duplicated alpha-globin genes in which ectopic recombination can lead to gene deletions, often very prevalent in populations affected by malaria, as well as reduplications. Here we show that spontaneous deletions can be accessed directly in genomic DNA by using single-DNA-molecule methods. These deletions proved to be remarkably common in both blood and sperm. Somatic deletions arise by a strictly intrachromosomal pathway of homologous exchange that also operates in the germ line and can generate mutational mosaicism, whereas sperm deletions frequently involve recombinational interactions between homologous chromosomes that most likely occur at meiosis. Ectopic recombination frequencies show surprisingly little requirement for long, identical homology blocks shared by paralogous sequences, and exchanges can occur even between short regions of sequence identity. Finally, direct knowledge of germ-line deletion rates can give insights into the fitness of individuals with these alpha-globin gene deletions, providing a new approach to investigating historical levels of selection operating in human populations.

DNA↗