Human Y Chromosome Variation

Myelodysplastic syndromes (MDS) share many features with acute myeloid leukemias (AML) and in fact 20 -40% of the patients eventually develop a picture of full blown AML. Chromosome 7 has been a focus of attention as a site harboring tumor suppressor genes whose loss of function contributes to leukemia transformation or tumor progression. Abnormalities of chromosome 7 are frequently encountered in AML and MDS. The aim of the present study was to detect the molecular abnormalities of chromosome 7 in Egyptian AML and MDS patients using the FISH technique and whether the abnormality has an implication on the prognosis of the disease after a period of one year follow up. Fluorescence in-situ hybridization (FISH) was performed for chromosome 7 using a locus specific probe for 7q31 and a centromeric probe from 7p11.1-q11.1 in a series of 30 patients diagnosed as: AML (20 patients) and MDS (10 patients) according to the FAB criteria. Aberrations of Chromosome 7 were found in 36.6% of AML patients: 3 cases showing monosomy with a mean positivity of 17.3%, 2 cases showing 7q deletion with a mean positivity of 11%. While both monosomy and deletion were detected in 3 cases. However, in MDS patients; monosomy for chromosome 7 was the only abnormality detected and was found in 30% of cases. Genetic abnormality of chromosome 7 showed a significant association with poor prognostic criteria. Patients who had normal FISH results showed a higher percentage (31.6%) of complete remission (CR) versus 0% in patients with monosomy or deletion who showed a higher percentage (100%) of death or poor response to therapy (NR). Although AML patients had a worse prognosis when compared to MDS patients, patients with genetic abnormalities showed the worst outcome.

the presence of multiple exostoses on the long bones. These exostoses are benign cartilaginous tumors (enchondromata). Three different EXT loci on chromosomes 8q (EXT1), 11p (EXT2) and 19p (EXT3) have been reported, and recently the EXT1 gene was identified by positional cloning. To isolate the EXT2 gene, we constructed a contig of yeast artificial chromosomes (YAC) and P1 clones covering the complete EXT2 candidate region on chromosome 11p11-p12. One of the transcribed sequences isolated from this region corresponds to a novel gene with homology to the EXT1 gene, and harbours inactivating mutations in different patients with hereditary multiple exostoses. This indicates that this gene is the EXT2 gene. EXT2 has an open reading frame encoding 718 amino acids with an overall homology of 30.9% with EXT1, suggesting that a family of related genes might be responsible for the development of EXT.

Approximately 8% of breast cancers show increased copy numbers of chromosome 17 centromere (CEP17) by fluorescence in situ hybridization (FISH) (ie average CEP17 >3.0 per nucleus). Currently, this pattern is believed to represent polysomy of chromosome 17. HER2‐amplified cancers have been shown to harbour complex patterns of genetic aberrations of chromosome 17, in particular involving its long arm. We hypothesized that aberrant copy numbers of CEP17 in FISH assays may not necessarily represent true chromosome 17 polysomy. Eighteen randomly selected CEP17 polysomic cases and a control group of ten CEP17 disomic cases, as defined by dual‐colour FISH, were studied by microarray‐based comparative genomic hybridization (aCGH), which was performed on microdissected samples using a 32K tiling‐path bacterial artificial chromosome microarray platform. Additional FISH probes were employed for SMS (17p11.2) and RARA (17q21.2) genes, as references for chromosome 17 copy number. Microarray‐b...

As a historical nomadic group in Central Asia, Kazaks have mainly inhabited the steppe zone from the Altay Mountains in the East to the Caspian Sea in the West. Fine scale characterization of the genetic profile and population structure of Kazaks would be invaluable for understanding their population history and modeling prehistoric human expansions across the Eurasian steppes. With this mind, we characterized the maternal lineages of 200 Kazaks from Jetisuu at mitochondrial genome level. Our results reveal that Jetisuu Kazaks have unique mtDNA haplotypes including those belonging to the basal branches of both West Eurasian (R0, H, HV) and East Eurasian (A, B, C, D) lineages. The great diversity observed in their maternal lineages may reflect pivotal geographic location of Kazaks in Eurasia and implies a complex history for this population. Comparative analyses of mitochondrial genomes of human populations in Central Eurasia reveal a common maternal genetic ancestry for Turko-Mongol...

Recent genome-wide association studies have identified a breast cancer susceptibility locus on 16q12 with an unknown biological basis. We used a set of single nucleotide polymorphism (SNP) markers to generate a fine-scale map and narrowed the region of association to a 133 kb DNA segment containing the largely uncharacterized hypothetical gene LOC643714, a short intergenic region and the 5 ′ end of TOX3. Re-sequencing this segment in European subjects identified 293 common polymorphisms, including a set of 26 highly correlated candidate causal variants. By evaluation of these SNPs in five breast cancer case -control studies involving more than 23 000 subjects from populations of European and Southeast Asian ancestry, all but 14 variants could be excluded at odds of <1:100. Most of the remaining variants lie in the intergenic region, which exhibits evolutionary conservation and open chromatin conformation, consistent with a regulatory function. African-American case -control studies exhibit a different pattern of association suggestive of an additional causative variant.

Mendez and colleagues reported the identification of a Y chromosome haplotype (the A00 lineage) that lies at the basal position of the Y chromosome phylogenetic tree. Incorporating this haplotype, the authors estimated the time to the most recent common ancestor (TMRCA) for the Y tree to be 338 000 years ago (95% CI ¼ 237 000-581 000). Such an extraordinarily early estimate contradicts all previous estimates in the literature and is over a 100 000 years older than the earliest fossils of anatomically modern humans. This estimate raises two astonishing possibilities, either the novel Y chromosome was inherited after ancestral humans interbred with another species, or anatomically modern Homo sapiens emerged earlier than previously estimated and quickly became subdivided into genetically differentiated subpopulations. We demonstrate that the TMRCA estimate was reached through inadequate statistical and analytical methods, each of which contributed to its inflation. We show that the authors ignored previously inferred Y-specific rates of substitution, incorrectly derived the Y-specific substitution rate from autosomal mutation rates, and compared unequal lengths of the novel Y chromosome with the previously recognized basal lineage. Our analysis indicates that the A00 lineage was derived from all the other lineages 208 300 (95% CI ¼ 163 900-260 200) years ago.

Complete or partial gain of the long arm of chromosome 17 (17q) has been shown recently by molecular cytogenetic techniques to be the most frequent chromosomal change in neuroblastoma and to be associated with adverse prognosis. Few reports, however, have focused on the precise mapping of the commonly overrepresented region. We have investigated 17q gain by the analysis of allelic imbalances at microsatellite loci dispersed along chromosome 17 in a series of 69 neuroblastomas. Allelic imbalances for at least two consecutive loci were observed in 39/59 informative cases, that is in agreement with previously reported frequencies of 17q gain. In a subset of the cases, comparative genomic hybridization analysis established the relationship between these allelic imbalances and the gain of 17q material. A partial 17q gain was observed in 9 cases, delineating a common region of 17q gain between the marker D17S787 (75 cM, 360 cR) and the telomere. In most cases, molecular results were suggestive of partial tri-or tetrasomy, whereas in 4 cases a higher copy number was documented. Our results also confirm that the presence of additional 17q material is closely associated with 1p36 deletion, MYCN amplification, and diploid or tetraploid chromosomal content.

This paper proposes a new hypothesis that challenges the prevailing view of Phoenician origins as strictly Levantine. Drawing from genetic, linguistic, and cultural evidence, it suggests that the Phoenicians may have descended from ancestral Semitic populations rooted in central Arabia, specifically the Najd region. Using the author's genetic data as a case study, the argument reconsiders Semitic migration patterns and proposes Najd as a potential cradle for early Phoenician ancestry. 6. Challenges and Opportunities-Current archaeological records do not link Najd directly to Phoenician settlements.-However, ongoing discoveries in Arabia (e.g., Dadan, Tayma) reveal urbanized cultures capable of long-distance influence.-Further interdisciplinary research (DNA, epigraphy, linguistics) is essential. 7. Conclusion This hypothesis does not deny the Levantine development of Phoenician civilization, but rather expands the lens through which their origins are viewed. The genetic data presented, coupled with cultural and linguistic parallels, suggest that Phoenician ancestry may extend deeper into the Arabian Peninsula than previously considered.

Abnormalities of chromosome 5 are common aberrations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), being del(5q) the most frequent. In contrast, monosomy 5 is not so frequent and, usually, is associated with complex karyotypes, conferring poor prognosis. The aim of this study was to analyze, by FISH for 5q31 (EGR1), a series of 28 MDS and AML cases with monosomy 5 detected by G-banding. FISH results revealed deletion of 5q31 in 24 of them (85.7%) and monosomy 5 just in three. FISH for 5q31 can complement conventional cytogenetics and improve the karyotype definition, leading to a better diagnostic and prognostic stratification.

Myelodysplastic syndromes (MDS) are poorly understood and rare hematologic malignancies in children. In recent years several germline mutations have been implicated in a subset of familial cases of MDS, other myeloid neoplasms, or bone marrow failure syndromes, including mutations in GATA2, ETV6, and DDX41 (1, 2). However, for some Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

The amount of genetic diversity in a population is determined by demographic and selection events in its history. Human populations which exhibit greatly reduced overall genetic diversity, presumably resulting from severe bottlenecks or founder events, are particularly interesting, not least because of their potential to serve as valuable resources for health studies. Here, we present an unexpected case, the human population of Nias Island in Indonesia, that exhibits severely reduced Y chromosome (non-recombining portion of the Y chromosome [NRY]) and to a lesser extent also reduced mitochondrial DNA (mtDNA) diversity as compared with most other populations from the Asia/Oceania region. Our genetic data, collected from more than 400 individuals from across the island, suggest a strong previously undetected bottleneck or founder event in the human population history of Nias, more pronounced for males than for females, followed by subsequent genetic isolation. Our findings are unexpected given the island's geographic proximity to the genetically highly diverse Southeast Asian world, as well as our previous knowledge about the human history of Nias. Furthermore, all NRY and virtually all mtDNA haplogroups observed in Nias can be attributed to the Austronesian expansion, in line with linguistic data, and in contrast with archaeological evidence for a pre-Austronesian occupation of Nias that, as we show here, left no significant genetic footprints in the contemporary population. Our work underlines the importance of human genetic diversity studies not only for a better understanding of human population history but also because of the potential relevance for genetic disease-mapping studies.

We report here a monosomy 7 transformation of donor cells following matched-unrelated, same sex, allogeneic bone marrow transplantation in a patient with severe congenital aplastic anemia. A PCR technique was employed to amplify microsatellite markers on chromosome 7 to confirm donor/recipient identity. We found that the transformation of monosomy 7 occurred in previously genetically normal donor cells. This study suggests that the microenvironment of the bone marrow of our patient with severe congenital aplastic anemia may have played a critical role in the development of monosomy 7 of normal donor cells and we conclude that chromosomal microsatellite marker analysis can be a valuable tool for precise donor/recipient differentiation in engraftment monitoring.

Health-related traits 5. Famous J individuals Eupedia Home > Genetics > Haplogroups (home) > Haplogroup J Haplogroup J (mtDNA) Author: Maciamo Hay. Originally published in January 2014. Last revised in September 2016 Haplogroup J is relatively evenly distributed across all Europe. The only population in which it is absent are the Saami from Lapland. The highest frequencies of mtDNA J in Europe are found in Cornwall (20%), Wales (15%), Iceland (14%), Denmark (13.5%), Sardinia (13%), Scotland (12.5%), England (11.5%), Switzerland (11.5%), the Netherlands (11%) and Romania (11%). In the Middle East, it is most common in Saudi Arabia (21%), followed by Kuwait (16%), Yemen (15%), Kurdistan (15%), south-west Iran (14%), Iraq (13%), and the United Arab Emirates (12%). Local peaks are also observed among some Caucasian ethnic groups, such as the North Ossetians (16%) and the Dargins (11%). The mutation defining haplogroup J is thought to have taken place some 45,000 years ago, probably in West Asia. It is estimated that J2 split first from J* around 37,000 years ago, followed by J1 some 33,000 years ago. Between the Last Glacial Maximum (c. 26,500 to 19,000 years before present) until the end of the last glaciation (c. 12,000 years ago), J lineages branched off in seven main subclades: J1b (± 23,000 ybp), J1c (± 16,500 ybp), J1d (± 20,000 ybp), J2a1 (± 16,500 ybp), J2a2 (± 20,500 ybp), J2b1 (± 15,500 ybp) and J2b2 (± 11,000 ybp). Note that the current nomenclature does not include any subclade called J1a anymore (the previous J1a was renamed J1b3a). Although no trace of mtDNA J has been found in Mesolithic or Palaeolithic Europe yet, it is likely that some J lineages recolonised Europe at the end of the glacial period from the Near Eastern refugia, as proposed by Pala et al. (2012) . If that is the case, this migration would most probably have been conducted by J2a1 lineages, a subclade that is virtually absent outside Europe today, although J1c cannot be excluded yet. The highest frequencies of J2a1 are found in northern Germany and Denmark (5%), Switzerland (3%) and England (2%). J1c being so rare in the Middle East today, it can be envisaged that it was a lineage of hunter-gatherers who inhabited the Eastern Mediterranean and southern Balkans during the Epipaleolithic, but that its diffusion across the rest of Europe did not take place until the Neolithic period.

DNA testing has shown that Y chromosome haplogroup R-U152/S28 and subclades are relatively common in eastern England today. They are known as "Alpine-Celtic" or "Italo-Celtic" based on the distribution across Europe as a whole. In seeking a likely source to explain the presence of this group in England, the author found that the Cimbri Tribe of what is today Jutland and nearby islands in Denmark was a likely candidate. Although residing deep within "Germanic" territory (Scandinavia), there is considerable evidence that they began as a Central and Southern European Celtic tribe, and their descendants may have been among those who moved to England during the major Medieval migrations. The following study, which began in 2006, will explore the historical, archaeological, linguistic and other data relating to the Cimbri. We will then take a "deep dive" into the DNA evidence, specifically relating to Y chromosome haplogroup R-U152/S28 and subclades. In 2023 this work was expanded to include haplogroup R-DF27/S250 and subclades, based on the findings of recent ancient DNA studies. This article is a work in progress, and will be updated as new data emerges. There are three specific hypotheses, noted as A, B and C which will be explored in order to explain when, and from where, R-U152/S28 and subclades as well as R-DF27/S250 and subclades arrived on the shores of what is today England and the British Isles.

Recent genome-wide association studies have identified a breast cancer susceptibility locus on 16q12 with an unknown biological basis. We used a set of single nucleotide polymorphism (SNP) markers to generate a fine-scale map and narrowed the region of association to a 133 kb DNA segment containing the largely uncharacterized hypothetical gene LOC643714, a short intergenic region and the 5 ′ end of TOX3. Re-sequencing this segment in European subjects identified 293 common polymorphisms, including a set of 26 highly correlated candidate causal variants. By evaluation of these SNPs in five breast cancer case -control studies involving more than 23 000 subjects from populations of European and Southeast Asian ancestry, all but 14 variants could be excluded at odds of <1:100. Most of the remaining variants lie in the intergenic region, which exhibits evolutionary conservation and open chromatin conformation, consistent with a regulatory function. African-American case -control studies exhibit a different pattern of association suggestive of an additional causative variant.

The Shetland Islands were settled by Norse Vikings beginning before 800 AD. There is no evidence that any of the original Pict occupiers of the Islands were still there when the Vikings arrived, and if they were there it appears the invaders may have "put them to the sword" since it is presumed that had some survived there would have at least been more than a handful of Celtic place names in all of the Islands. In addition, the Shetland Islands were staging areas for Norse Viking raids to Scotland, Ireland, the west coast of England, and the Isle of Mann. Some sort of peaceful coexistence of the Picts and the warlike Vikings in such a small area does not seem likely. In the year 1468 Norway deeded Shetland to Scotland, and soon Scots began arriving as lairds, merchants, clergy and generally assumed positions in the upper ranks of society-leaving the most of the original Norse settlers to tend to small farms known as crofts where they raised a small amount of grain, tended herds of sheep, fished, participated in whaling expeditions, and later large numbers joined the Merchant Navy. Here we explore the Y-DNA and autosomal DNA evidence which demonstrates the Scandinavian origins of the Gilbert Basil Williamson family from Mid Yell, Shetland Islands.

Down syndrome (DS) is due to the presence of an extra full or partial chromosome 21 (Hsa21). The identification of genes contributing to DS pathogenesis could be the key to any rational therapy of the associated intellectual disability. We aim at generating quantitative transcriptome maps in DS integrating all gene expression profile datasets available for any cell type or tissue, to obtain a complete model of the transcriptome in terms of both expression values for each gene and segmental trend of gene expression along each chromosome. We used the TRAM (Transcriptome Mapper) software for this meta-analysis, comparing transcript expression levels and profiles between DS and normal brain, lymphoblastoid cell lines, blood cells, fibroblasts, thymus and induced pluripotent stem cells, respectively. TRAM combined, normalized, and integrated datasets from different sources and across diverse experimental platforms. The main output was a linear expression value that may be used as a reference for each of up to 37,181 mapped transcripts analyzed, related to both known genes and expression sequence tag (EST) clusters. An independent example in vitro validation of fibroblast transcriptome map data was performed through "Real-Time" reverse transcription polymerase chain reaction showing an excellent correlation coefficient (r = 0.93, p < 0.0001) with data obtained in silico. The availability of linear expression values for each gene allowed the testing of the gene dosage hypothesis of the expected 3:2 DS/normal ratio for Hsa21 as well as other human genes in DS, in addition to listing genes differentially expressed with statistical significance. Although a fraction of Hsa21 genes escapes dosage effects, Hsa21 genes are selectively over-expressed in DS samples compared to genes from other chromosomes, reflecting a decisive role in the pathogenesis of the syndrome. Finally, the analysis of chromosomal segments reveals a high prevalence of Hsa21 over-expressed segments over the other genomic regions, suggesting, in particular, a specific region on Hsa21 that appears to be frequently over-expressed (21q22). Our complete datasets are released as a new framework to investigate transcription in DS for individual genes as well as chromosomal segments in different cell types and tissues.

Cysteine/tyrosine-rich 1 (CYYR1) is a gene we previously identified on human chromosome 21 starting from an in-depth bioinformatics analysis of chromosome 21 segment 40/105 (21q21.3), where no coding region had previously been predicted. CYYR1 was initially characterized as a four-exon gene, whose brain-derived cDNA sequencing predicts a 154-amino acid product. In this study we provide, with in silico and in vitro analyses, the first detailed description of the human CYYR1 locus. The analysis of this locus revealed that it is composed of a multitranscript system, which includes at least seven CYYR1 alternative spliced isoforms and a new CYYR1 antisense gene (named CYYR1-AS1). In particular, we cloned, for the first time, the following isoforms: CYYR1-1,2,3,4b and CYYR1-1,2,3b, which present a different 3 0 transcribed region, with a consequent different carboxy-terminus of the predicted proteins; CYYR1-1,2,4 lacks exon 3; CYYR1-1,2,2bis,3,4 presents an additional exon between exon 2 and exon 3; CYYR1-1b,2,3,4 presents a different 5 0 untranslated region when compared to CYYR1. The complexity of the locus is enriched by the presence of an antisense transcript. We have cloned a long transcript overlapping with CYYR1 as an antisense RNA, probably a non-coding RNA. Expression analysis performed in different normal tissues, tumour cell lines as well as in trisomy 21 and euploid fibroblasts has confirmed a quantitative and qualitative variability in the expression pattern of the multi-transcript locus, suggesting a possible role in complex diseases that should be further investigated.

the presence of multiple exostoses on the long bones. These exostoses are benign cartilaginous tumors (enchondromata). Three different EXT loci on chromosomes 8q (EXT1), 11p (EXT2) and 19p (EXT3) have been reported, and recently the EXT1 gene was identified by positional cloning. To isolate the EXT2 gene, we constructed a contig of yeast artificial chromosomes (YAC) and P1 clones covering the complete EXT2 candidate region on chromosome 11p11-p12. One of the transcribed sequences isolated from this region corresponds to a novel gene with homology to the EXT1 gene, and harbours inactivating mutations in different patients with hereditary multiple exostoses. This indicates that this gene is the EXT2 gene. EXT2 has an open reading frame encoding 718 amino acids with an overall homology of 30.9% with EXT1, suggesting that a family of related genes might be responsible for the development of EXT.

Background. Complex chromosomal rearrangements are rare events compatible with survival, consisting in imbalance and/or position effect, which contribute to a range of clinical pictures. The investigation and diagnosis of these cases is often difficult and knowing the methodology followed in similar cases can be very useful for others. The interpretation of the results does not always lead to the mechanism’s identification and can potentially create critical communication problems for a possible recurrence. Here, we investigated two carriers of complex abnormality of chromosome 7 with a severe clinical picture. Case presentation. The first case was a 2-year-old girl with a pathological phenotype. Conventional cytogenetics evidenced a duplication of part of the short arm of chromosome 7. By array-CGH analysis we found a complex situation with three discontinuous trisomy regions (7p22.1p21.3, 7p21.3, 7p21.3p15.3). The second case was a newborn investigated for hypo development and dys...

The characterization of mitochondrial DNA (mtDNA) allows the establishment of genetic structures and phylogenetic relationships in human populations, tracing lineages far back in time. We analysed samples of mtDNA from twenty (20) Native American populations (700 individuals) dispersed throughout Colombian territory. Samples were collected during 1989-1993 in the context of the program Expedición Humana ("Human Expedition") and stored in the Biological Repository of the Institute of Human Genetics (IGH) at the Pontificia Universidad Javeriana (Bogotá, Colombia). Haplogroups were determined by analysis of RFLPs. Most frequent was haplogroup A, with 338 individuals (48.3%). Haplogroup A is also one of the most frequent haplogroups in Mesoamerica, and we interpret our finding as supporting models that propose Chibchan-speaking groups migrated to northern Colombia from Mesoamerica in prehistoric times. Haplogroup C was found in 199 individuals (28.4%), while less frequent were B and D, with 113 and 41 (16% and 6%) individuals, respectively. The haplogroups of nine ( ) individuals (1.3%) could not be determined due to the low quality of the samples of DNA. Although all the sampled populations had genetic structures that fit broadly into the patterns that might be expected for contemporary Central and South American indigenous groups, it was found that haplogroups A and B were more frequent in northern Colombia, while haplogroups C and D were more frequent in southern and south-western Colombia.

HIGHLIGHTS  Amerindian ancestry has model the CTG distribution at DMPK gene of Mexican Mestizos.  Haplotype analysis supports the hypothesis of an ancestral DM1 mutation in Mexico.  Both European and Amerindian ancestry might have introduced the disease to Mexico.

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The Canary Islands were settled in the first millennium AD by colonizers likely originating from North Africa. The settlers developed a farming economy with barley as the main crop. Archaeological evidence suggests the islands then remained isolated until European sea-travellers discovered and colonized them during the 14 th and 15 th centuries. Here we report a population study of ancient DNA from twenty-one archaeobotanical barley grains from Gran Canaria dating from 1050 to 1440 cal AD. The material showed exceptional DNA preservation and genotyping was carried out for 99 single nucleotide markers. In addition 101 extant landrace accessions from the Canary Islands and the western Mediterranean were genotyped. The archaeological material showed high genetic similarity to extant landraces from the Canary Islands. In contrast, accessions from the Canary Islands were highly differentiated from both Iberian and North African mainland barley. Within the Canary Islands, landraces from the easternmost islands were genetically differentiated from landraces from the western islands, corroborating the presence of pre-Hispanic barley cultivation on Lanzarote. The results demonstrate the potential of population genetic analyses of ancient DNA. They support the hypothesis of an original colonization, possibly from present day Morocco, and subsequent isolation of the islands and reveal a farmer fidelity to the local barley that has lasted for centuries.

The Canary Islands were settled in the first millennium AD by colonizers likely originating from North Africa. The settlers developed a farming economy with barley as the main crop. Archaeological evidence suggests the islands then remained isolated until European sea-travellers discovered and colonized them during the 14 th and 15 th centuries. Here we report a population study of ancient DNA from twenty-one archaeobotanical barley grains from Gran Canaria dating from 1050 to 1440 cal AD. The material showed exceptional DNA preservation and genotyping was carried out for 99 single nucleotide markers. In addition 101 extant landrace accessions from the Canary Islands and the western Mediterranean were genotyped. The archaeological material showed high genetic similarity to extant landraces from the Canary Islands. In contrast, accessions from the Canary Islands were highly differentiated from both Iberian and North African mainland barley. Within the Canary Islands, landraces from the easternmost islands were genetically differentiated from landraces from the western islands, corroborating the presence of pre-Hispanic barley cultivation on Lanzarote. The results demonstrate the potential of population genetic analyses of ancient DNA. They support the hypothesis of an original colonization, possibly from present day Morocco, and subsequent isolation of the islands and reveal a farmer fidelity to the local barley that has lasted for centuries.

We performed microarray analyses in AML with trisomies 8 (n ¼ 12), 11 (n ¼ 7), 13 (n ¼ 7), monosomy 7 (n ¼ 9), and deletion 5q (n ¼ 7) as sole changes to investigate whether genomic gains and losses translate into altered expression levels of genes located in the affected chromosomal regions. Controls were 104 AML with normal karyotype. In subgroups with trisomy, the median expression of genes located on gained chromosomes was higher, while in AML with monosomy 7 and deletion 5q the median expression of genes located in deleted regions was lower. The 50 most differentially expressed genes, as compared to all other subtypes, were equally distributed over the genome in AML subgroups with trisomies. In contrast, 30 and 86% of the most differentially expressed genes characteristic for AML with 5q deletion and monosomy 7 are located on chromosomes 5 or 7. In conclusion, gain of whole chromosomes leads to overexpression of genes located on the respective chromosomes. Losses of larger regions of the genome translate into lower expression of the majority of genes represented by only one allele. The reduced expression of these genes is the most characteristic difference in gene expression profiles between AML with monosomy 7 and AML with deletion 5q, respectively, and other AML subtypes. Therefore, these data provide evidence that gene dosage effects gene expression in AML with unbalanced karyotype abnormalities. Losses of specific regions of the genome determine the gene expression profile more strongly than the gain of whole chromosomes.

Chromosome analysis of short-term culture of a basal cell carcinoma showed five clonal chromosome abnormalities, t(9;14)(q12 or q13;p11), del(1)(q23 or q25), trisomy 5, trisomy 7, and monosomy X. In addition, several nonclonal structural and numerical changes were seen in the tumor cells.

Background. Complex chromosomal rearrangements are rare events compatible with survival, consisting in imbalance and/or position effect, which contribute to a range of clinical pictures. The investigation and diagnosis of these cases is often di cult and knowing the methodology followed in similar cases can be very useful for others. The interpretation of the results does not always lead to the mechanism's identi cation and can potentially create critical communication problems for a possible recurrence. Here, we investigated two carriers of complex abnormality of chromosome 7 with a severe clinical picture. Case presentation. The rst case was a 2-year-old girl with a pathological phenotype. Conventional cytogenetics evidenced a duplication of part of the short arm of chromosome 7. By array-CGH analysis we found a complex situation with three discontinuous trisomy regions (7p22.1p21.3, 7p21.3, 7p21.3p15.3). The second case was a newborn investigated for hypo development and dysmorphism. His karyotype showed a structurally altered chromosome 7. The maternal karyotype evidenced a structurally rearranged chromosome 7: the long arm region (7q11.23q22) was inserted in the short arm, at 7p15.3. The array-CGH analysis on the child identi ed an even more complex picture with a trisomic region at 7q11.23q22 and a tetrasomic region of 4.5 Mb, between the 7q21.3 and the q22.1. The maternal array-CGH evidenced a trisomic portion corresponding to the tetrasomic region of the boy. Conclusions. Our work demonstrated, once again, that the support of both techniques is necessary to correctly interpret complex rearrangements. Finally, searching the literature and with bioinformatic tools, we found that segmental duplications, short interspersed elements (SINE) and long interspersed elements (LINE), may be responsible for these complex rearrangements.

The predisposition of monosomy 7 to diabetes insipidus (DI) in acute myeloid leukemia (AML) led us to ask whether AML associated with monosomy 7 and DI will differ from AML associated with other karyotype aberrations and DI and whether the outcome of patients with AML and DI will differ from those without DI. We describe 2 patients from Roswell Park Cancer Institute and discuss 29 additional cases from the literature. AML with monosomy 7 and DI (n 5 25) had a trend towards a lower complete remission (p 5 0.0936) and worse survival (p 5 0.0480) than AML with other karyotype changes and DI (n 5 6). Further, AML with monosomy 7 and DI had worse complete remission rate and overall survival than AML with monosomy 7 but without DI. In conclusion, it appears that AML with monosomy 7 and DI is a disease entity with specifically poor outcome.

Monosomy 7 [−7] and/or partial loss of chromosome 7 [del(7q)] are associated with poor and intermediate prognosis, respectively, in myelodysplastic syndromes (MDS), but somatic mutations may also play a key complementary role. We analyzed the impact on the outcomes of deep targeted mutational screening in 280 MDS patients with −7/del(7q) as isolated cytogenetic abnormality (86 with del(7q) and 194 with −7). Patients with del(7q) or −7 had similar demographic and diseaserelated characteristics. Somatic mutations were detected in 79% (93/117) of patients (82% in −7 and 73% in del(7q) group). Median number of mutations per patient was 2 (range 0-8). There was no difference in mutation frequency between the two groups. Patients harbouring ≥2 mutations had a worse outcome than patients with <2 or no mutations (leukaemic transformation at 24 months, 38% and 20%, respectively, p = 0.044). Untreated patients with del(7q) had better overall survival (OS) compared with −7 (median OS, 34 vs 17 months, p = 0.034). In multivariable analysis, blast count, TP53 mutations and number of mutations were independent predictors of OS, whereas the cytogenetic subgroups did not retain prognostic relevance. This study highlights the importance of mutational analysis in terms of prognosis in MDS patients with isolated −7 or del(7q).

rat eDNA clone encoding a portion of phosphateactivated glutaminase was used to identify DNA restriction fragment length polymorphisms (RFLPs) in sets of somatic cell hybrids and between wild-derived and inbred strains of mice. Segregation of rat and mouse chromosomes among somatic cell hybrids indicated assignment to rat chromosome 9 and mouse chromosome 1. Analysis of chromosome 1 alleles for several genes in an interspecific cross between Mus sprefus and C3H/HeJ-&d/&d mice indicates that glutaminase can be positioned within 5.5 2 2.0 CM proximal to Ctla-4. Similarly, human-hamster somatic cell hybrids were examined for RFLPs, and four human EcoRI restriction fragments were found to hybridize with the rat glutaminase probe. Two of these restriction fragments cosegregated and mapped to human chromosome 2 in a region that is syntenic with mouse chromosome 1 and rat chromosome 9. ra 198s Academic PrtxwJ, Inc.

This report presents two rare cases, one of paediatric myelodysplastic syndrome (MDS) and the other juvenile chronic myeloid leukaemia (jCML). In the first case, there were clinical and biological features of MDS-refractory anaemia with excess blasts (RAEB). The bone marrow (BM) karyotype demonstrated a monosomy 7 which was confirmed by fluorescence in situ hybridization (FISH). In addition, FISH analysis showed that an a-satellite DNA sequence had been transferred from chromosomes 13/21 to one homologue of chromosomes 22. The BCR-ABL rearrangement was negative. In the second case, at diagnosis, the karyotype was 46,XX. FISH analysis with the simultaneous and individual application of abl and bcr probes for chromosome 9 and 22, respectively, revealed the presence of the BCR-ABL rearrangement in addition to an extra ABL sequence locating chromosome 20. A clone that was BCR-ABL gene rearrangement negative but with an extra ABL DNA sequence on chromsome 20, and another clone that was BCR-ABL gene rearrangement negative were detected by DC-FISH and uni-colour (UC-) FISH analysis. No monosomy 7 was detected by conventional cytogenetic or FISH analyses.

Bulleted statements What's already known about this topic?  Acquired erythropoietic uroporphyria associated with myeloid malignancy is a rare porphyria characterized by increased levels of isomer I porphyrin in a typical CEP pattern, but do not harbour UROS germline mutations and the enzymatic UROS activity in erythrocytes is normal.  Typically is associated to myelodysplastic syndrome.  Less than 10 cases of erythropoietic uroporphyria secondary to MDS have been described in the literature. What does this study add?  This is the first reported case of non-congenital erythropoietic uroporphyria secondary to MDS with a karyotype showing the presence of a derivative chromosome 3, suspected to be the result of an inversion involving the 3q21-3q26 chromosomal regions.

The c-mos and c-rnyc proto-oncogenes have been assigned to bands q22 and q24, respectively, of human chromosome No. 8. A gain of chromosome No. 8 is the most common abnormality observed in myeloproliferative diseases. By using probes specific for the c-mos and c-rnyc genes, we have analysed the genomic DNA from peripheral blood and bone marrow samples from 15 patients with various malignant myeloid diseases, including leukemia and myelodysplasia, and from one patient with non-Hodgkin's lymphoma, all of whom have trisomy for chromosome No. 8. Except for one patient, the c-mos and c-rnyc genes were found in restriction fragments of germline size. In one patient with myelodysplasia, one c-myc allele was rearranged in a Hind III fragment, the other allele being normal. Thus, trisomy 8 associated with human hematologic neoplasia is generally not related to gross rearrangements of the c-mos or c-rnyc genes.

The c-mos and c-rnyc proto-oncogenes have been assigned to bands q22 and q24, respectively, of human chromosome No. 8. A gain of chromosome No. 8 is the most common abnormality observed in myeloproliferative diseases. By using probes specific for the c-mos and c-rnyc genes, we have analysed the genomic DNA from peripheral blood and bone marrow samples from 15 patients with various malignant myeloid diseases, including leukemia and myelodysplasia, and from one patient with non-Hodgkin's lymphoma, all of whom have trisomy for chromosome No. 8. Except for one patient, the c-mos and c-rnyc genes were found in restriction fragments of germline size. In one patient with myelodysplasia, one c-myc allele was rearranged in a Hind III fragment, the other allele being normal. Thus, trisomy 8 associated with human hematologic neoplasia is generally not related to gross rearrangements of the c-mos or c-rnyc genes.

Down syndrome (DS) is due to the presence of an extra full or partial chromosome 21 (Hsa21). The identification of genes contributing to DS pathogenesis could be the key to any rational therapy of the associated intellectual disability. We aim at generating quantitative transcriptome maps in DS integrating all gene expression profile datasets available for any cell type or tissue, to obtain a complete model of the transcriptome in terms of both expression values for each gene and segmental trend of gene expression along each chromosome. We used the TRAM (Transcriptome Mapper) software for this meta-analysis, comparing transcript expression levels and profiles between DS and normal brain, lymphoblastoid cell lines, blood cells, fibroblasts, thymus and induced pluripotent stem cells, respectively. TRAM combined, normalized, and integrated datasets from different sources and across diverse experimental platforms. The main output was a linear expression value that may be used as a reference for each of up to 37,181 mapped transcripts analyzed, related to both known genes and expression sequence tag (EST) clusters. An independent example in vitro validation of fibroblast transcriptome map data was performed through "Real-Time" reverse transcription polymerase chain reaction showing an excellent correlation coefficient (r = 0.93, p < 0.0001) with data obtained in silico. The availability of linear expression values for each gene allowed the testing of the gene dosage hypothesis of the expected 3:2 DS/normal ratio for Hsa21 as well as other human genes in DS, in addition to listing genes differentially expressed with statistical significance. Although a fraction of Hsa21 genes escapes dosage effects, Hsa21 genes are selectively over-expressed in DS samples compared to genes from other chromosomes, reflecting a decisive role in the pathogenesis of the syndrome. Finally, the analysis of chromosomal segments reveals a high prevalence of Hsa21 over-expressed segments over the other genomic regions, suggesting, in particular, a specific region on Hsa21 that appears to be frequently over-expressed (21q22). Our complete datasets are released as a new framework to investigate transcription in DS for individual genes as well as chromosomal segments in different cell types and tissues.

BackgroundThe Y chromosome polymorphism has been widely studied for human migrations, population genetics, forensic applications, and paternity analysis. However, studies regarding genetic lineage and population genetic structure of the Y chromosome in different regions of Saudi Arabia are limited.AimThis study aimed to analyze the distribution of Y chromosome haplotypes in a sample of 125 native Saudi males from different geographic regions of Saudi Arabia and compare to previously published Y chromosome haplotype data from Saudi Arabia and some neighboring Arab populations.Materials and methodsBuccal swabs were collected from 125 healthy unrelated native Saudi males from different geographic regions of Saudi Arabia. Genomic DNA was extracted by Chelex®100; 17 Y-STR loci were amplified using the AmpFℓlSTR Yfiler PCR amplification kit and detected on the 3130 Genetic AnalyzerTM. Allele frequency and gene diversity were calculated with online tool STRAF. The Saudi population data wer...

The indigenous population of the Canary Islands, which colonized the archipelago around the 3rd century CE, provides both a window into the past of North Africa and a unique model to explore the effects of insularity. We generate genome-wide data from 40 individuals from the seven islands, dated between the 3rd–16rd centuries CE. Along with components already present in Moroccan Neolithic populations, the Canarian natives show signatures related to Bronze Age expansions in Eurasia and trans-Saharan migrations. The lack of gene flow between islands and constant or decreasing effective population sizes suggest that populations were isolated. While some island populations maintained relatively high genetic diversity, with the only detected bottleneck coinciding with the colonization time, other islands with fewer natural resources show the effects of insularity and isolation. Finally, consistent genetic differentiation between eastern and western islands points to a more complex coloni...

Differentiating male lineages using non-recombining Y-chromosomal genetic markers is highly informative for tracing human migration and for forensic studies. Recently, it has been shown that the level of male lineage resolution can be enhanced by analysing rapidly mutating (RM) Y-STRs. The aim of this study was to develop an allelic frequency database for Qatari population to evaluate the resolution power of 13 RM Y-STRs. The overall haplotype diversity (HD) was 100%. It was found that the markers which contributed the most toward high HD were DYF399S1 and DYF403S1a/b. Together with their value for paternal male relative differentiation, these RM Y-STRs will be a valuable asset for forensic casework. AMOVA test was performed between Qatari population in comparison to Gulf countries, Middle East, and several worldwide population data sets. FST values were also calculated. Geography was found to account considerably for the pattern of population sub structuring. The RM Y-STR markers showed remarkable haplotype resolution power in the Qatari population, high gene diversity and sufficient robustness for a diverse range of applications. 2015 Published by Elsevier Ireland Ltd.

Differentiating male lineages using non-recombining Y-chromosomal genetic markers is highly informative for tracing human migration and for forensic studies. Recently, it has been shown that the level of male lineage resolution can be enhanced by analysing rapidly mutating (RM) Y-STRs. The aim of this study was to develop an allelic frequency database for Qatari population to evaluate the resolution power of 13 RM Y-STRs. The overall haplotype diversity (HD) was 100%. It was found that the markers which contributed the most toward high HD were DYF399S1 and DYF403S1a/b. Together with their value for paternal male relative differentiation, these RM Y-STRs will be a valuable asset for forensic casework. AMOVA test was performed between Qatari population in comparison to Gulf countries, Middle East, and several worldwide population data sets. FST values were also calculated. Geography was found to account considerably for the pattern of population sub structuring. The RM Y-STR markers showed remarkable haplotype resolution power in the Qatari population, high gene diversity and sufficient robustness for a diverse range of applications. 2015 Published by Elsevier Ireland Ltd.

Východiska: Nízkostupňové gliomy představují heterogenní skupinu primárních mozkových nádorů. Jejich současná dia gnostika je založena hlavně na histologické klasifi kaci. S rozvojem molekulární cytogenetiky však bylo objeveno několik markerů umožňujících lépe defi novat daný gliomový subtyp. Cílem studie bylo sledovat získané chromozomové aberace v buňkách nízkostupňových gliomů molekulárně cytogenetickými metodami a hledat nové genomové změny, které by mohly souviset s progresí nádoru. Soubor pacientů a metody: Technikami interfázní fl uorescenční in situ hybridizace (I-FISH) a single nucleotide polymorphism (SNP) array jsme vyšetřili vzorky od 41 pacientů s histologicky potvrzenými nízkostupňovými gliomy (19 žen a 22 mužů, medián věku 42 let). Výsledky: Kromě nejčastější známé aberace, tj. kombinované delece krátkých ramen chromozomu 1 a dlouhých ramen chromozomu 19 (u 81,25 % pacientů), jsme u pacientů s oligodendrogliomy detekovali další rekurentní aberace-delece krátkých a/ nebo dlouhých ramen chromozomu 4 (25 % nemocných), delece krátkých ramen chromozomu 9 (18,75 % pacientů), delece dlouhých ramen chromozomu 13 a monozomii chromozomu 18 (18,75 % pacientů). U pacientů s astrocytomy jsme často pozorovali deleci krátkých ramen chromozomu 1 (24 % nemocných), amplifi kaci dlouhých ramen chromozomu 7 (16 % nemocných), deleci dlouhých ramen chromozomu 13 (20 % nemocných), segmentální uniparentální disomii (UPD) na krátkých ramenech chromozomu 17 (60 % pacientů) a deleci dlouhých ramen chromozomu 19 (28 % nemocných). U jednoho pacienta jsme pozorovali tzv. chromothripsis chromozomu 10. Závěr: V pilotní studii jsme kombinací metod I-FISH a SNP array detekovali nejen známé chromozomové změny, které jsou typické pro jednotlivé subtypy nádorů, ale také nové nebo méně časté rekurentní aberace. Jejich úlohu v progresi nádorových buněk, stejně jako jejich význam z hlediska klasifi kace nízkostupňových gliomů však bude nezbytné ověřit v dalších studiích na větších souborech nemocných.

Human Y chromosome haplogroup J1-M267 is a common male lineage in West Asia. One high-frequency region—encompassing the Arabian Peninsula, southern Mesopotamia, and the southern Levant—resides ~ 2000 km away from the other one found in the Caucasus. The region between them, although has a lower frequency, nevertheless demonstrates high genetic diversity. Studies associate this haplogroup with the spread of farming from the Fertile Crescent to Europe, the spread of mobile pastoralism in the desert regions of the Arabian Peninsula, the history of the Jews, and the spread of Islam. Here, we study past human male demography in West Asia with 172 high-coverage whole Y chromosome sequences and 889 genotyped samples of haplogroup J1-M267. We show that this haplogroup evolved ~ 20,000 years ago somewhere in northwestern Iran, the Caucasus, the Armenian Highland, and northern Mesopotamia. The major branch—J1a1a1-P58—evolved during the early Holocene ~ 9500 years ago somewhere in the Arabian ...

As a historical nomadic group in Central Asia, Kazaks have mainly inhabited the steppe zone from the Altay Mountains in the East to the Caspian Sea in the West. Fine scale characterization of the genetic profile and population structure of Kazaks would be invaluable for understanding their population history and modeling prehistoric human expansions across the Eurasian steppes. With this mind, we characterized the maternal lineages of 200 Kazaks from Jetisuu at mitochondrial genome level. Our results reveal that Jetisuu Kazaks have unique mtDNA haplotypes including those belonging to the basal branches of both West Eurasian (R0, H, HV) and East Eurasian (A, B, C, D) lineages. The great diversity observed in their maternal lineages may reflect pivotal geographic location of Kazaks in Eurasia and implies a complex history for this population. Comparative analyses of mitochondrial genomes of human populations in Central Eurasia reveal a common maternal genetic ancestry for Turko-Mongol...

Although the human Y chromosome has effectively shown utility in uncovering facets of human evolution and population histories, the ascertainment bias present in early Y-chromosome variant data sets limited the accuracy of diversity and TMRCA estimates obtained from them. The advent of next-generation sequencing, however, has removed this bias and allowed for the discovery of thousands of new variants for use in improving the Y-chromosome phylogeny and computing estimates that are more accurate. Here, we describe the high-coverage sequencing of the whole Y chromosome in a data set of 19 male Khoe-San individuals in comparison with existing whole Y-chromosome sequence data. Due to the increased resolution, we potentially resolve the source of haplogroup B-P70 in the Khoe-San, and reconcile recently published haplogroup A-M51 data with the most recent version of the ISOGG Y-chromosome phylogeny. Our results also improve the positioning of tentatively placed new branches of the ISOGG Y...

We have performed a comparative study of allelic imbalances in human and murine osteosarcomas to identify genetic changes critical for osteosarcomagenesis. Two adjacent but discrete loci on mouse chromosome 9 were found to show high levels of allelic imbalance in radiationinduced osteosarcomas arising in (BALB/c6CBA/CA) F1 hybrid mice. The syntenic human chromosomal regions were investigated in 42 sporadic human osteosarcomas. For the distal locus (OSS1) on mouse chromosome 9 the syntenic human locus was identified on chromosome 6q14 and showed allelic imbalance in 77% of the cases. Comparison between the human and mouse syntenic regions narrowed the locus down to a 4 Mbp fragment flanked by the marker genes ME1 and SCL35A1. For the proximal locus (OSS2) on mouse chromosome 9, a candidate human locus was mapped to chromosome 15q21 in a region showing allelic imbalance in 58% of human osteosarcomas. We have used a combination of synteny and microsatellite mapping to identify two potential osteosarcoma suppressor gene loci. This strategy represents a powerful tool for the identification of new genes important for the formation of human tumors.

Purpose: Trastuzumab is the cornerstone for treatment of women with HER2-overexpressing breast cancer, both in the adjuvant and in the metastatic settings. The accurate assessment of HER2 is, therefore, critical to identifying patients who may benefit from trastuzumab-based therapy. This project aimed to determine the optimal scoring method for fluorescence in situ hybridization (FISH) assay. Methods: FISH assay was done on 893 samples of breast cancer. Three scoring methods were evaluated: Her2/CEP17≥2, Her2&gt;4, or Her2&gt;6. Protein and gene expression were evaluated by immunohistochemistry (n = 584) and mRNA/assay/nucleic acid sequence–based amplification (NASBA; n = 90). Results: Samples were divided into five groups based on FISH results: disomic amplified and nonamplified, polysomic amplified, nonamplified, and discordant (10.8% of cases, mostly positive with Her2&gt;4 scoring, but negative with the others). Her2/CEP17≥2 and Her2&gt;6 scoring methods showed the best associat...