Analysis of polymorphism of the hypervariable locus of the apolipoprotein-B gene in populations of the Volga-Ural region

Data on the allelic polymorphism at the hypervariable locus 3' to the apolipoprotein B gene (apo B) in seven Turkic and Finno-Ugric human populations of the Volga-Ural region obtained by means of PCR method are presented. Sixteen allelic variants were distinguished, and the frequency distribution of alleles and genotypes across the populations studied were estimated. Alleles 34 and 36 appeared to be more common (from 13 to 45% in different populations); the calculated heterozygosity indices ranged from 59.3 to 73.4%. Comparison of the data with that on other world populations made it possible to deduce some specific features of the alleles frequency distribution associated with geographic position of the population.     

Analysis of factor VIII gene polymorphisms in Brazilian blacks reveals further differences in the black population

We report here the analysis of four intragenic (BclI, HindIII, XbaI, and BglI) and two extragenic (MspI and TaqI/St14) polymorphisms associated with the factor VIII gene in the Brazilian Black population. No difference was observed for the allelic frequencies of the BclI, HindIII, and BglI polymorphisms when we compared our results with those reported for North American Blacks. For the first time, the XbaI and MspI polymorphisms were investigated in a Black population. Interestingly, the XbaI polymorphism is almost monomorphic for the Brazilian Black population, differing in this respect from all other populations studied thus far. The MspI polymorphism presents inverse allelic frequencies for the Brazilian Blacks when compared with Caucasians, as observed for the BclI and HindIII polymorphisms. Analysis of the TaqI/St14 multiallelic system revealed five novel alleles (ranging from 5.8 to 11.0 kb) which may represent unique alleles for the Black population. The results show that analysis of factor VIII gene polymorphisms and haplotypes may be successfully used for investigating interrelationships between human populations. The results also allow definition of a strategy for carrier detection and prenatal diagnosis of hemophilia A in this population based on analysis of factor VIII gene polymorphisms, which is considered an alternative approach for those families where identification of gene mutation is not feasible.     

New amino acid polymorphism, Ala/Val4058, in exon 45 of the polycystic kidney disease 1 gene: evolution of alleles

The PKD1 gene, which is responsible for the most common form of autosomal dominant polycystic kidney disease, has recently been cloned and sequenced. Many disease-causing mutations have been characterized in this gene, most of them resulting in premature protein termination. However, mutation analysis not routinely implemented for family investigations in a clinical setting, because of the large size and complexity of the gene. Instead, genetic linkage analysis using highly polymorphic CA dinucleotide repeats that map around the gene is still the method of choice. Recently, a few intragenic polymorphisms have been described that are also useful for linkage studies. Here, a new diallelic polymorphism is described for amino acid residue 4058, Ala/Val4058, with allelic frequencies of 0.88 and 0.12, respectively, and a heterozygosity of 0.23, in the Greek and Greek-Cypriot populations. Interestingly, this polymorphism and Ala4091-A/G, which has previously been described in Caucasians, were not detected in DNA from 44 Japanese samples tested. This is particularly important when allelic frequencies in a particular population are used for linkage analysis of families of different ethnic origin. Also, observation of the two polymorphisms together as haplotypes suggests that the Ala/Val4058 polymorphism occurred more recently than the establishment of the Ala4091-A/G polymorphism, and specifically on the G allele.     

Spondyloarthropathies and HLA-B27 subtypes in the populations of the Russian North

The aim of the study was to investigate the role of HLA-B27 subtypes in development of ankylosing spondylitis and other seronegative spondylarthropathies. Using oligotyping techniques we studied native DNA of 219 HLA-B27 positive natives: 88 Chukotka residents and 131 Mordovians (Russian Ugro-Finnish population). Only subtypes HLA-B*2705 and B*2702 were revealed. A dominant subtype of HLA-B27 among the natives was HLA-B*2705: 99% among residents of Chukotka and 86% among Mordovians. It was established that among spondylarthropathic patients the frequency of B*2705 does not differ from its incidence in the studied populations. The data support the suggestion that several B27 subtypes and common genetic determinant of B27 gene may be involved in pathogenesis of spondylarthropathy.     

Studies of the effects of inhaled magnesium on airway reactivity to histamine and adenosine monophosphate in asthmatic subjects

HLA class II DRB1-DQA1-DQB1 haplotypic polymorphism was determined in 120 Liberian and 230 Gabonese individuals. In our study groups, the number of allelic variants observed for each locus was similar to that found in non-African populations. However, 39 novel haplotypes and several yet unrecognized DRB1-DQA1 and DQA1-DQB1 combinations were identified. The extent of HLA-haplotypic variability in Africans appears to result from the high degree of allele combinations rather than from allelic polymorphism.     

Allelic diversity at the merozoite surface protein-1 (MSP-1) locus in natural Plasmodium falciparum populations: a brief overview

The merozoite surface protein-1 (MSP-1) locus of Plasmodium falciparum codes for a major asexual blood-stage antigen currently proposed as a major malaria vaccine candidate. The protein, however, shows extensive polymorphism, which may compromise its use in sub-unit vaccines. Here we compare the patterns of allelic diversity at the MSP-1 locus in wild isolates from three epidemiologically distinct malaria-endemic areas: the hypoendemic southwestern Brazilian Amazon (n = 54), the mesoendemic southern Vietnam (n = 238) and the holoendemic northern Tanzania (n = 79). Fragments of the variable blocks 2, 4a, 4b and 6 or 10 of this single-copy gene were amplified by the polymerase chain reaction, and 24 MSP-1 gene types were defined as unique combinations of allelic types in each variable block. Ten different MSP-1 types were identified in Brazil, 23 in Vietnam and 13 in Tanzania. The proportion of genetically mixed infections (isolates with parasites carrying more than one MSP-1 version) ranged from 39% in Brazil to 44% in Vietnam and 60% in Tanzania. The vast majority (90%) of the typed parasite populations from Brazil and Tanzania belonged to the same seven most frequent MSP-1 gene types. In contrast, these seven gene types corresponded to only 61% of the typed parasite populations from Vietnam. Non-random associations were found between allelic types in blocks 4a and 6 among Vietnamese isolates, the same pattern being observed in independent studies performed in 1994, 1995 and 1996. These results suggest that MSP-1 is under selective pressure in the local parasite population. Nevertheless, the finding that similar MSP-1 type frequencies were found in 1994 and 1996 argues against the prominence of short-term frequency-dependent immune selection of MSP-1 polymorphisms. Non-random associations between MSP-1 allelic types, however, were not detected among isolates from Brazil and Tanzania. A preliminary analysis of the distribution of MSP-1 gene types per host among isolates from Tanzania, but not among those from Brazil and Vietnam, shows significant deviation from that expected under the null hypothesis of independent distribution of parasites carrying different gene types in the human hosts. Some epidemiological consequences of these findings are discussed.     

Allelic frequencies of twelve dinucleotide repeat marker loci on chromosome 13 in the normal Japanese population

To establish a genotypic database for dinucleotide repeat marker loci in the Japanese population, we determined allelic frequencies of 12 such markers on chromosome 13 and compared them with data from Caucasians in the GDB archive. The average heterozygosity (79%) for the 12 loci was the same for the two populations. However, allelic distributions at two of the marker loci were quite different. These data will be useful for disease studies in the Japanese population that involve linkage or sibship-pair analyses, or association studies.     

Medico-genetic study of residents of Marii El republic: burden of hereditary diseases in four regions of the republic

A medical genetic study of Orshanskii, Morkinskii, Sovetskii, and Semurskii raions (districts) of the Marii El Republic was performed. The total number of subjects examined was 115,743. Meadow Maris and Russians accounted for the most part of the populations of the districts studied. A total of 147 families with presumably autosomal dominant (AD) pathology and 150 families with presumably autosomal recessive (AR) or X-linked pathology (270 and 169 affected persons, respectively) were revealed. Segregation analysis demonstrated a good agreement between the observed and expected segregation frequencies for both AR and AD diseases, as well as a considerable number of sporadic cases of presumably AD diseases. The incidence of hereditary diseases was estimated separately for different population groups. Significant differences in this incidence were revealed between the urban and rural, as well as between the Russian and Mari populations; the average incidence was 2.33 affected subjects per 1000 people. The incidence of AR diseases was significantly higher in Maris than in Russians (1.34 x 10(-3) and 0.82 x 10(-3), respectively). The populations studied exhibited a significant, high correlation between the incidence of AR diseases and the levels of random and local inbreeding. The incidence of X-linked recessive diseases was approximately the same as in Russian populations studied earlier. Its average value was 0.5 per 1000 men; the incidence in the Mari and Russian populations did not differ significantly. The higher AD incidence in the total population studied and the higher AR incidence in the Meadow Mari population compared to the populations studied earlier are discussed.     

Expression of lactate dehydrogenase, myosin heavy chain and myogenic regulatory factor genes in rabbit embryonic muscle cell cultures

Polymorphisms of cytochrome P450 genes show pronounced interethnic variation and have not been previously studied in the South-Amerindian population, which probably has an Asian origin. Therefore, a similar distribution of allelic and haplotype frequencies of cytochrome P450 genes to Asian populations might be expected in South-Amerindians. We analysed the allelic frequencies and haplotype distribution for CYP2D6, CYP1A1 and CYP2E1 genes in the South-Amerindian population of Chile (Mapuche, n = 84) by Southern blot or polymerase chain reaction-restriction fragment length polymorphism. Similar allelic frequencies and haplotype distribution for the CYP2E1 gene between Mapuches and Asian populations were observed. Frequencies of the two major functional CYP2D6*1 and CYP2D6*2 alleles and the CYP2D6*5 null allele were similar to most populations world-wide. The alleles CYP2D6*3 and *9, absent in Asians, were not found in Mapuches. The CYP2D6*4 allelic group, uncommon in Asian populations, had a low frequency in Mapuches (0.036). However, the CYP2D6*10 allele (Ch1, Ch2 and J), highly frequent in Asians (0.33-0.50), had a very low frequency (0.018) in our study population. In addition, the presence of the common Chinese 44 kb XbaI fragment of CYP2D6 (0.19-0.31 in Asians) was not detected in South-Amerindians. Interestingly, high frequencies for the rare m2 and Val alleles of the CYP1A1 gene were found in Mapuches (0.821 and 0.91, respectively), and the rare Val/m2 haplotype was significantly higher in Mapuches (0.748) than in Asians (0.24) (P < 0.01). The frequency of this haplotype in Mapuches is the highest frequency reported to date. The population studied was in Hardy-Weinberg equilibrium for these polymorphisms. The major differences between Mapuches and Asians were for CYP2D6*10 and CYP1A1 allelic frequencies, as well as the absence of the common Chinese 44 kb XbaI fragment of CYP2D6. These differences might be interpreted as a consequence of genetic drifts caused by a founder effect in the settlement of South-Amerindians, or genetic selection caused by dietary or environmental factors.     

Pax7 includes two polymorphic homeoboxes which contain rearrangements associated with differences in the ability to regenerate damaged skeletal muscle in adult mice

Pax7 is a paired-type homeobox gene which has previously been shown to play an important role in skeletal muscle formation. It is expressed in skeletal muscle of the limbs during embryogenesis and in adulthood. The aims of this study were firstly to determine the degree of polymorphism of Pax7 amongst inbred laboratory mice using Southern blotting and Pax7 regional specific sub-probes. Secondly, functional studies were performed on mice with each of the different structural forms of Pax7 to determine whether they were associated with differences in the ability to regenerate damaged skeletal muscle. Four different allelic forms of Pax7 have now been identified in laboratory mice indicating that the previously reported DNA sequence of Pax7 is not applicable to all laboratory mice. Hybridisation patterns of TaqI digested DNA representing each of the different Pax7 alleles with the Pax7 specific sub-probes suggested that in contrast to previous findings, Pax7 is associated with two highly polymorphic homeoboxes. The presence of two homeoboxes in BALB/c mice has been confirmed by DNA sequencing. Results of functional studies have also shown that the ability to regenerate damaged skeletal muscle in adult mice is strongly associated with the presence of a 0.15-kb TaqI fragment derived from one of the homeoboxes.     

Global patterns of linkage disequilibrium at the CD4 locus and modern human origins

Haplotypes consisting of alleles at a short tandem repeat polymorphism (STRP) and an Alu deletion polymorphism at the CD4 locus on chromosome 12 were analyzed in more than 1600 individuals sampled from 42 geographically dispersed populations (13 African, 2 Middle Eastern, 7 European, 9 Asian, 3 Pacific, and 8 Amerindian). Sub-Saharan African populations had more haplotypes and exhibited more variability in frequencies of haplotypes than the Northeast African or non-African populations. The Alu deletion was nearly always associated with a single STRP allele in non-African and Northeast African populations but was associated with a wide range of STRP alleles in the sub-Saharan African populations. This global pattern of haplotype variation and linkage disequilibrium suggests a common and recent African origin for all non-African human populations.     

Genetic relationships among Japanese, northern Han, Hui, Uygur, Kazakh, Greek, Saudi Arabian, and Italian populations based on allelic frequencies at four VNTR (D1S80, D4S43, COL2A1, D17S5) and one STR (ACTBP2) loci

The genetic polymorphism at four variable number of tandem repeats (D1S80, D4S43, COL2A1, D17S5) and one short tandem repeat (ACTBP2) loci was assessed by polymerase chain reaction analysis of genomic DNA obtained from blood samples of eight human populations (Japanese, Northern Han, Hui, Uygur, Kazakh, Saudi Arabian, Greek, Italian). Allele frequencies at all loci were in the Hardy-Weinberg equilibrium for each population. With the exception of ACTBP2, the allelic distribution patterns for these loci revealed a marked genetic divergence among the eight populations. A dendrogram constructed by the neighbor-joining method based on the allele frequencies of the five loci suggested that the five Asian populations (Japanese, Northern Han, Hui, Uygur, and Kazakh) formed one cluster, whereas the two European populations and one West Asian population (Italian, Greek, and Saudi Arabian) formed another. The genetic relationship among these populations may have been greatly influenced by admixture as a result of the migration of individuals along the Silk Road throughout history.     

Factor VII polymorphisms in populations with different risks of cardiovascular disease

Increased plasma factor VII coagulant activity (FVII:C) has been associated with the risk of ischemic heart disease (IHD). Differences in plasma FVII:C among individuals are associated with three common polymorphisms in the FVII gene. Therefore, we investigated FVII polymorphisms in four populations that differ in their risk of developing cardiovascular disease, namely, Europeans, Greenland Inuit, Gujarati Indians, and Afrocaribbeans. We studied (1) the promoter polymorphism, which is the result of a decanucleotide insertion in the FVII promoter at position -323 from the start of translation; (2) the hypervariable region 4 polymorphism (HVR4), which is the result of a variable number of tandem repeats in intron 7; and (3) the RQ353 polymorphism, a guanine-to-adenine substitution in the position of the codon for amino acid 353 resulting in an amino acid replacement of arginine (R) by glutamine (Q) in the FVII protein. The frequencies of these three polymorphisms and their linkage disequilibrium were different in the four populations studied. The frequencies of the alleles associated with higher plasma FVII:C were lower in the Europeans than in the Inuit, a population with a lower incidence of IHD. There was an association between both the promoter polymorphism and the RQ353 polymorphism and the plasma FVII:C in the Europeans, the Inuit, and the Gujarati Indians, and an association only between the RQ353 polymorphism and plasma FVII:C in the Afrocaribbeans. Only in the Inuit was the HVR4 polymorphism associated with plasma FVII:C. In multiple regression analysis, the additional information provided by the promoter polymorphism when the other polymorphisms were already included in the model was the most pronounced, suggesting that the promoter polymorphism may be the functional mutation having the greatest effect on determining plasma FVII:C.     

Role of the kdr and super-kdr sodium channel mutations in pyrethroid resistance: correlation of allelic frequency to resistance level in wild and laboratory populations of horn flies (Haematobia irritans)

The kdr and super-kdr point mutations found in the insect sodium channel gene are postulated to confer knockdown resistance (kdr) to pyrethroids. Using an allele-specific PCR assay to detect these mutations in individual horn flies, Haematobia irritans (L.), we determined the allelic frequency of the kdr and super-kdr mutations in several wild and laboratory populations. Wild populations with very similar allelic frequencies had resistance levels that ranged widely from 3- to 18-fold relative to a susceptible population. Conversely, the kdr allele frequency in a lab population with 17-fold resistance was nearly double that found in a heavily pressured wild population with 18-fold resistance. We conclude that, although the kdr mutation confers significant levels of pyrethroid resistance, a substantial component of resistance in insecticidally pressured populations is conferred by mechanisms that are PBO-suppressible. High super-kdr allele frequencies were detected in two resistant lab populations, but in wild populations with equivalent resistance the super-kdr allele frequency was very low. Interestingly, in over 1200 individuals assayed, the super-kdr mutation was never detected in the absence of the kdr mutation.     

Analysis of DNA polymorphism detected by genomic fingerprinting based on phage M13 DNA, in populations of Bashkir and Komi

Hyperpolymorphism of minisatellite DNA, detected using the M13 bacteriophage DNA hybridization probe, was studied in three ethnographic groups of Bashkirs and in the Komi population. Bands from 2 to 20 kb were analyzed in hybridization patterns. A significant population difference was detected both in evaluation of the average number of hybridization fragments per individuals and in the distribution of frequency of some fractions. Thus, it seems possible to describe a set of so-called characteristic fractions for each population. According to the hybridization fragment frequency for the populations investigated, an index of genetic similarity was calculated. The possibility of using this kind of multiple polymorphism of DNA in population genetic investigations at the level of ethnic groups and peoples is discussed, and a conclusion is made about the necessity of searching for the most informative methods of analyzing the data obtained.     

Association of a monoamine oxidase B allele with Parkinson's disease

Monoamine oxidase B (MAO-B) is implicated in the cause of Parkinson's disease (PD) because of its role in metabolizing the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and forming H2O2 during dopamine metabolism. Altered MAO-B activity has been observed in PD platelets. Polymerase chain reaction was used to amplify a portion of the MAO-B gene. Polymerase chain reaction products were screened with restriction enzymes to identify fragments useful for single-stranded conformational polymorphism analysis. A single-stranded conformational polymorphism was identified in an MAO-B polymerase chain reaction product after Hae III digestion. One hundred twenty-one control individuals were allelotyped with frequencies of 0.45 and 0.55 for alleles 1 and 2, respectively. Frequencies of 0.62 and 0.38 (1 and 2, respectively) were observed in a population of 46 patients with PD. The presence of MAO-B allele 1 is associated with a relative risk for PD of 2.03-fold (confidence interval, 1.44-2.61; p < 0.02). For comparison, a monoamine oxidase A polymorphism was used to determine allelic frequencies in these same populations and no statistically significant differences were found. These results suggest that an inherited variant of MAO-B may be involved in a genetic predisposition for PD.     

Common amino acid substitutions in insulin receptor substrate-4 are not associated with Type II diabetes mellitus or insulin resistance

The family of insulin receptor substrates (IRS1-4) is defined by proteins with an overall similar structure. IRS-1 and IRS-2 have been shown to have key roles in cellular transmission of the action of insulin, insulin-like growth factor-1 and various cytokines. We have previously identified amino acid polymorphisms in the human IRS-1 and IRS-2 proteins. Given the documented importance of IRS-1 and -2 in insulin signalling and the implications of distribution of these genes for the pathogenesis of insulin resistance and diabetes, we decided that the most recently identified member of the IRS family, IRS-4, was a relevant candidate to examine for genetic variability which might be associated with subsets of diabetes or insulin resistance. The gene encoding IRS-4 was analysed by the single strand conformation polymorphism technique in 83 Danish Caucasians with Type II (non-insulin-dependent) diabetes mellitus. Five amino acid polymorphisms were identified: Leu34Phe, Arg411Gly, Gly584Cys, His879Asp and Lys883Thr. In an association study of 324 patients with Type II diabetes and 267 control subjects with normal glucose tolerance the polymorphism at codon 34 was found with allelic frequencies of 3.9 and 2.3 %, respectively, the variant at codon 411 with allelic frequencies of 3.9 and 5.6%, respectively, and the variant at codon 879 with frequencies of 19.2 and 18.0%, respectively. Each carrier of the codon 34 polymorphism was also a carrier of the codon 411 and codon 879 variants and similarly, carriers of the variant at codon 411 were also carriers of the polymorphism at codon 879. The variants at codon 584 and 883 were each found in only one Type II diabetic patient. The allelic frequencies of the variants at codon 411 and 879 were also determined in 380 young healthy subjects (4.6 and 18.1 %, respectively). The insulin sensitivity index as estimated by Bergman's minimal model of the young healthy subjects carrying either polymorphism was indistinguishable from the carriers of wild-type IRS-4. Moreover, none of the men were heterozygous for the IRS-4 polymorphisms indicating that the gene is located on the X-chromosome. In conclusion, amino acid polymorphisms in human IRS-4 are common in Caucasians but are not associated with Type II diabetes or with insulin resistance in young healthy subjects.     

Overlapping genomic sequences: a treasure trove of single-nucleotide polymorphisms

An efficient strategy to develop a dense set of single-nucleotide polymorphism (SNP) markers is to take advantage of the human genome sequencing effort currently under way. Our approach is based on the fact that bacterial artificial chromosomes (BACs) and P1-based artificial chromosomes (PACs) used in long-range sequencing projects come from diploid libraries. If the overlapping clones sequenced are from different lineages, one is comparing the sequences from 2 homologous chromosomes in the overlapping region. We have analyzed in detail every SNP identified while sequencing three sets of overlapping clones found on chromosome 5p15.2, 7q21-7q22, and 13q12-13q13. In the 200.6 kb of DNA sequence analyzed in these overlaps, 153 SNPs were identified. Computer analysis for repetitive elements and suitability for STS development yielded 44 STSs containing 68 SNPs for further study. All 68 SNPs were confirmed to be present in at least one of the three (Caucasian, African-American, Hispanic) populations studied. Furthermore, 42 of the SNPs tested (62%) were informative in at least one population, 32 (47%) were informative in two or more populations, and 23 (34%) were informative in all three populations. These results clearly indicate that developing SNP markers from overlapping genomic sequence is highly efficient and cost effective, requiring only the two simple steps of developing STSs around the known SNPs and characterizing them in the appropriate populations.     

Interlocking nailing--unreamed, reamed?]

OBJECTIVE: To investigate the relationships between the A-G point mutation at position -3826 bp in the 5' flanking domain of the uncoupling protein 1 (UCP1 A-3826G) and some obesity phenotypes in the Swedish Obese Subjects (SOS) cohorts of obese and non-obese men and women. Previous studies have supported the hypothesis of an association between the UCP1 A-3826G polymorphism and body weight regulation in humans. DESIGN: Case-control study comparing obese subjects from the SOS registry and a sample of the Swedish general population (body mass index (BMI) <27 kg/m2) with respect to genotype and allele frequencies of the UCP1 A-3826G polymorphism. SUBJECTS: A total of 985 Swedish subjects including 674 obese (310 Male; 364 Female) and 311 non-obese subjects (54 Male; 257 Female) from the SOS cohorts. MEASUREMENTS: DNA was extracted from total blood and genotyped by PCR-RFLP. Obesity-related phenotypes include weight history for SOS obese cohort and current weight, BMI, waist circumference and waist to hip ratio (WHR) for obese and normal weight subjects. RESULTS: No significant difference in the allelic frequencies between obese and non-obese subjects (0.25 vs 0.24; P = 0.67). In both genders, current weight, BMI, waist circumference, WHR and weight gain over time (either measures of maximal weight ever achieved minus weight at 20 y or current weight minus weight at 20 y) were similar in carriers and non-carriers of the UCP1 A-3826G mutation (P>0.05). Similar results were obtained when the three genotypes were compared. CONCLUSIONS: In contrast to what was found in other populations, the UCP1 A-3826G sequence variation is not associated with obesity-related phenotypes and weight gain over time in subjects from the SOS cohorts.     

Chromosome 7 rearrangements in glioblastomas; loci adjacent to EGFR are independently amplified

The first gene found to be amplified in human glioblastomas was EGFR at 7p12. More recently the MET gene at 7q31 was also reported amplified. We have studied chromosome 7 in a series of 47 glioblastomas by FISH, RFLP and microsatellite analysis. Four per cent (2/47) had 1 centromere, 26% (12/47) 2, 32% (15/47) 3, 4% (2/47) 4, and 34% (16/47) had subpopulations with variable numbers of chromosome 7 centromeres. In 25 of the 47 tumors (53%) the pattern of allelic imbalance observed at each informative locus was similar and in accord with the FISH data, indicating loss or gain of complete chromosome copies. In 32% of tumors (15/47) varying allelic imbalance was seen at different loci along the chromosome indicative of loss or gain of parts of chromosome 7 on a background of disomy, trisomy, tetrasomy, or polysomy. Amplification was studied in an extended series of 121 glioblastomas, and was seen at the 7p12 region in 47 tumors (39%). Forty-two tumors showed amplification of EGFR and 12 of these had extensive amplicons including a number of adjacent loci, always involving only 1 allele. The amplicons of 5 tumors (11%) did not include EGFR, indicating that other unidentified genes in the region are targeted for amplification. Amplification of MET was not found. The findings show that copy number changes of chromosome 7 are common and that a number of genes may be targeted for amplification at 7p12 in glioblastomas.