Biomedical subjects

G E Novick

Publications and source records attributed to G E Novick.

9 recordsLinked to original sources

PubMed1998

Effects of Alu insertions on gene function.

Alu elements are a family of short interspersed repetitive elements (SINEs) found exclusively in primates. These elements are around 300 base pairs long, are found in excess of one million copies per diploid genome, and are dispersed throughout the human genome. Alu elements are scattered by a mechanism called "retrotransposition". Three independent steps are involved in retrotransposition: transcription of the Alu repetitive element, reverse transcription of the Alu RNA and integration of the Alu cDNA. The fact that Alu elements retrotranspose so readily suggests that they have a myriad of effects on the genome, mostly by inactivating genes or altering their function. These characteristics of Alu repetitive elements point to these repetitive DNA fragments as a major driving force for evolution. In addition, Alu elements are known to adopt diverse functions depending on the context of the surrounding genetic material into which they insert. In this article, we review some of the evidence that demonstrates the functional significance of Alu repeats.

Alu Elements↗

PubMed1998

Polymorphic Alu insertions and the Asian origin of Native American populations.

A rapid PCR-based assay was used to study the distribution of 5 polymorphic Alu insertions in 895 unrelated individuals from 30 populations, 24 from North, Central, and South America. Although a significant level of interpopulation variability was detected, the variability was less than that observed in a worldwide population survey. This is consistent with the bottleneck effect and genetic drift forces that may have acted on the migrating founder groups. The results corroborate the Asian origin of native American populations but do not support the multiple-wave migration hypothesis supposedly responsible for the tri-partite Eskaleut, Nadene, and Amerind linguistic groups. Instead, these populations exhibit three major identifiable clusters reflecting geographic distribution. Close similarity between the Chinese and native Americans suggests recent gene flow from Asia.

Americas↗

PubMed1997

Distribution of HLA-DQA1 alleles in Arab and Pakistani individuals from Dubai, United Arab Emirates.

PCR-based typing of the HLA-DQA1 locus, using allele specific oligonucleotide (ASO) probes and reverse dot blot methodology was used to determine allelic distributions and construct a database for Arab and Pakistani individuals living in Dubai. Genotype and allelic frequencies were calculated, and the data were tested for departures from Hardy-Weinberg (HWE) equilibrium. The most frequent HLA-DQA1 alleles among Dubaian Arabs are DQA1 4 and 1.2. Among Pakistanis, the most frequent allele is also DQA1 4. No significant deviations from HWE were detected.

Alleles↗

PubMed1997

Effects of subpopulation structure on probability calculations of DNA profiles from forensic PCR analysis.

DNA typing for forensic identification is a two-step process. The first step involves determining the profiles of samples collected at the crime scene and comparing them with the profiles obtained from suspects and the victims. In the case of a match that includes the suspect as the potential source of the material collected at the crime scene, the last step in the process is to answer the question, what is the likelihood that someone in addition to the suspect could match the profile of the sample studied? This likelihood is calculated by determining the frequency of the suspect's profile in the relevant population databases. The design of forensic databases and the criteria for comparison has been addressed by the NRC report of 1996 (National Research Council, 1996). However, the fact that geographical proximity, migrational patterns, and even cultural and social practices have effects on subpopulation structure establishes the grounds for further study into its effects on the calculation of probability of occurrence values. The issue becomes more relevant in the case of discrete polymorphic markers that show higher probability of occurrence in the reference populations, where several orders of magnitude difference between the databases may have an impact on the jury. In this study, we calculated G values for all possible pairwise comparisons of allelic frequencies in the different databases from the races or subpopulations examined. In addition, we analyzed a set of 24 unrelated Caucasian, 37 unrelated African-American, and 96 unrelated Sioux/Chippewa individuals for seven polymorphic loci (DQA1, LDLR, GYPA, HBGG, D7S8, GC, and D1S80). All three sets of individuals where sampled from Minnesota. The probability of occurrence for all seven loci were calculated with respect to nine different databases: Caucasian, Arabic, Korean, Sioux/Chippewa, Navajo, Pueblo, African American, Southeastern Hispanic, and Southwestern Hispanic. Analysis of the results demonstrated marked differences in the probabilities of occurrence when individuals were compared to the different populations and subpopulation databases. The possible genetic and forensic consequences of subpopulation structure on probability calculations are discussed.

DNA Fingerprinting↗

PubMed1997

Distribution of HLA-DQ alpha and polymarker (LDLR, GC, GYPA, HBGG, and D7S8) alleles in Arab and Pakistani populations living in Abu Dhabi, United Arab Emirates.

Randomly collected blood samples from 100 Arabs and 100 Pakistanis residing in Abu Dhabi were analyzed using the HLA-DQ alpha and polymarker (LDLR, GC, GYPA, HBGG, D7S8) PCR based reverse dot blot systems. Allelic frequencies for each allele and observed heterozygosity for each locus were calculated. Departures from Hardy-Weinberg expectations (HWE) were determined using the unbiased estimate of the expected homozygote/ heterozygote frequencies, the likelihood ratio test and the exact test. No significant departures from HWE expectations were detected.

Blood Proteins↗

PubMed1995

Polymorphic human specific Alu insertions as markers for human identification.

Alu sequences represent the largest family of short interspersed repetitive elements (SINEs) in humans with 500 000 copies per genome. Recently, one Alu subfamily was found to be human specific (HS). We originally described the use of polymorphis HS Alu insertions as a tool in population studies and recently as tools in DNA fingerprinting and forensic analysis. In this report, we will use this simple polymerase chain reaction (PCR) base technique for the detection of HS Alu insertion polymorphisms. We will test the resolving power of this DNA profiling approach in both population genetics and paternity assessment. At the population level, we will describe the genotypic distribution of five polymorphic Alu insertions among 3 populations from the American continent, one of African origin, the other two Amerindians. Insight into their relationships will be provided. At the family level, we will examine one European American family of seven individuals and the same pedigree will also be characterized by way of the two systems currently and widely used to ascertain paternity: PCR-sequence specific oligonucleotide probe hybridization (PCR-SSO) and PCR-restriction fragment length polymorphism (PCR-RFLP) of human leucocyte antigen (HLA) class II molecules, and a standard RFLP protocol used in forensic casework and paternity studies. The importance and strengths of the methods as well as its perspectives for future use in filiation studies will be evaluated.

Forensic Medicine↗

PubMed1994

African origin of human-specific polymorphic Alu insertions.

Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few "master" genes. Among the 500,000 Alu elements in the human genome are members of the human-specific subfamily that are not fixed in the human species; that is, not all chromosomes carry an Alu element at a particular locus. Four such polymorphic human-specific Alu insertions were analyzed by a rapid, PCR-based assay that uses primers that flank the insertion point to determine genotypes based on the presence or absence of the Alu element. These four polymorphic Alu insertions were shown to be absent from the genomes of a number of nonhuman primates, consistent with their arising as human genetic polymorphisms sometime after the human/African ape divergence. Analysis of 664 unrelated individuals from 16 population groups from around the world revealed substantial levels of variation within population groups and significant genetic differentiation among groups. No significant associations were found among the four loci, consistent with their location on different chromosomes. A maximum-likelihood tree of population relationships showed four major groupings consisting of Africa, Europe, Asia/Americas, and Australia/New Guinea, which is concordant with similar trees based on other loci. A particularly useful feature of the polymorphic Alu insertions is that the ancestral state is known to be the absence of the Alu element, and the presence of the Alu element at a particular chromosomal site reflects a single, unique event in human evolution. A hypothetical ancestral group can then be included in the tree analysis, with the frequency of each insertion set to zero. The ancestral group connected to the maximum-likelihood tree within the African branch, which suggests an African origin of these polymorphic Alu insertions. These data are concordant with other diverse data sets, which lends further support to the recent African origin hypothesis for modern humans. Polymorphic Alu insertions represent a source of genetic variation for studying human population structure and evolution.

Africa↗

PubMed1993

The use of polymorphic Alu insertions in human DNA fingerprinting.

We have characterized several Human Specific (HS) Alu insertions as either dimorphic (TPA25, PV92, APO), slightly dimorphic (C2N4 and C4N4) or monomorphic (C3N1, C4N6, C4N2, C4N5, C4N8) based on studies of Caucasian, Asian, American Black and African Black populations. Our approach is based upon: 1) PCR amplification using primers complementary to the unique DNA sequences that flank the site of insertion of the different Alu elements studied; 2) gel electrophoresis and scoring according to the presence or absence of an Alu insertion in one or both homologous chromosomes; 3) allele frequencies determined by gene counting and compared to Hardy-Weinberg expectations. Our DNA fingerprinting procedure using PCR amplification of diallelic polymorphic (dimorphic) Human Specific Alu insertions, may be used as a tool for genetic mapping, to characterize populations, study human migrational patterns, and track the inheritance of human genetic disorders.

DNA Fingerprinting↗

PubMed1992

Genome canalization: the coevolution of transposable and interspersed repetitive elements with single copy DNA.

Transposable and interspersed repetitive elements (TIREs) are ubiquitous features of both prokaryotic and eukaryotic genomes. However, controversy has arisen as to whether these sequences represent useless 'selfish' DNA elements, with no cellular function, as opposed to useful genetic units. In this review, we selected two insect species, the Dipteran Drosophila and the Lepidopteran Bombyx mori (the silkmoth), in an attempt to resolve this debate. These two species were selected on the basis of the special interest that our laboratory has had over the years in Bombyx with its well known molecular and developmental biology, and the wealth of genetic data that exist for Drosophila. In addition, these two species represent contrasting repetitive element types and patterns of distribution. On one hand, Bombyx exhibits the short interspersion pattern in which Alu-like TIREs predominate while Drosophila possesses the long interspersion pattern in which retroviral-like TIREs are prevalent. In Bombyx, the main TIRE family is Bm-1 while the Drosophila group contains predominantly copia-like elements, non-LTR retroposons, bacterial-type retroposons and fold-back transposable elements sequences. Our analysis of the information revealed highly non-random patterns of both TIRE biology and evolution, more indicative of these sequences acting as genomic symbionts under cellular regulation rather than useless or selfish junk DNA. In addition, we extended our analysis of potential TIRE functionality to what is known from other eukaryotic systems. From this study, it became apparent that these DNA elements may have originated as innocuous or selfish sequences and then adopted functions. The mechanism for this conversion from non-functionality to specific roles is a process of coevolution between the repetitive element and other cellular DNA often times in close physical proximity. The resulting interdependence between repetitive elements and other cellular sequences restrict the number of evolutionarily successful mutational changes for a given function or cistron. This mutual limitation is what we call genome canalization. Well documented examples are discussed to support this hypothesis and a mechanistic model is presented for how such genomic canalization can occur. Also proposed are empirical studies which would support or invalidate aspects of this hypothesis.

Animals↗