Human personal genome sequencing can be done with high efficiency by aligning a huge number of short reads derived from various next generation sequencing (NGS) technologies to the reference genome sequence. One of the major obstacles is the incompleteness of human reference genome. We tried to analyze the effect of hidden gene duplication on the NGS data using the known example of hydin gene. Hydin2 , a duplicated copy of hydin on chromosome 16q22, has been recently found to be localized to chromosome 1q21, and is not included in the current version of standard human genome reference. We found that all of eight personal genome data published so far do not contain hydin2, and there is large number of nsSNPs in hydin. The heterozygosity of those nsSNPs was significantly higher than expected. The sequence coverage depth in hydin gene was about two fold of average depth. We believe that these unique finding of hydin can be used as useful indicators to discover new hidden multiplication in human genome.
Coat Protein Complex I ; Gene Duplication ; Genome ; Genome, Human ; Humans

Factor VIII/genetics* ; Gene Duplication ; Humans ; Male ; Thrombosis/genetics*

Gene dosage determination is increasingly important for the study of both genome variation and rearrangement associated with complex diseases. Large genomic duplications and deletions are increasingly found as the causes. Methods such as PCR or sequencing are usually qualitative rather than quantitative. Thus, these methods can not detect large genomic duplications or deletions. Therefore, searching for a gene dosage method which is reliable, sensitive and high-throughput becomes imperative. Many high-performance technologies have been developed for gene dosage analyses in the recent years. There are generally three categories of methods including cytogenetic, Southern or dot blotting, or PCR amplification. Recent development in these techniques have been introduced and discussed in this review, which will help people to choose a suitable method for different research.
Blotting, Southern ; methods ; Cytogenetic Analysis ; methods ; Gene Deletion ; Gene Dosage ; genetics ; Gene Duplication ; Humans ; Polymerase Chain Reaction ; methods

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.
Drug Design* ; Gene Duplication ; Genetic Association Studies ; Genome ; Genomics* ; Humans ; Ligands ; Neuropeptides* ; Vertebrates

Congenital leukemia is very rare, and its prevalence according to recently published papers is from 1 to 5 per million live births. This can be often diagnosed in postpartum throughout bone marrow biopsy, showing abnormal proliferation of immature blasts and granulocytic precursors. Hepatosplenomegaly is the most common feature which is found during perinatal examinations, that diagnosing is difficult during perinatal period. Hepatosplenomegaly can occur not only in congenital leukemia but in many other cases such as infection which is the most common cause. In other words, congenital leukemia is the one of the rare causes of hepatosplenomegaly. However, this case shows the fetus with the features of hepatosplenomegaly during perinatal period and being diagnosed as congenital leukemia associated with acquired AML1 gene duplication in postpartum through bone marrow biopsy. Due to its rare instance, we are to describe the case with a review of literatures.
Biopsy ; Bone Marrow ; Fetus* ; Gene Duplication* ; Leukemia* ; Live Birth ; Postpartum Period ; Prevalence

In the research field of quality control in Chinese medicinal materials, variation in active ingredients of medicinal plant is always the key and hot issues. With the development of high-throughput sequencing technologies and reducing cost, a large numbers of genes from medicinal plant were cloning and provide a solid foundation for further research of gene structure and its biological function, and also provides conditions for explore active ingredient variation and its quality control from the perspective of molecular pharmacognosy. This paper introduces the concept of homologous gene, gene duplication and classification. We prospect the function of duplicated genes in the role of molecular mechanism research about variation in active ingredients, aiming at providing a new way for medicinal materials quality control.
Drugs, Chinese Herbal ; analysis ; Gene Duplication ; Plant Proteins ; genetics ; Plants, Medicinal ; chemistry ; genetics ; Quality Control

Theoretically, microduplication of chromosomal region 22q11.2, which is rich in segmental duplications, should be as frequent as microdeletions of the same region. Preliminary analysis on the rarity of reports for 22q11.2 microduplication in the literature has suggested that, for the discovery of 22q11.2 microduplication, there has been a lack of sensitivity for routine diagnostic techniques such as karyotyping, PCR and FISH. On the other hand, the diverse anomalies and extremely variable phenotypes of carriers also implied great difficulties one has to face upon clinical consultation. Genetics as well as clinical problems in connection with 22q11.2 microduplication has vividly illustrated the great challenge for the interpretation of genotype-phenotype correlation, and thereby posed yet another gray zone for clinical genetics research.
Chromosome Deletion ; Chromosomes, Human, Pair 22 ; genetics ; Gene Duplication ; Genetics, Medical ; Humans ; Phenotype

OBJECTIVE: To report on a case with severe hemophilia A (HA) due to a large duplication of F8 gene. METHODS: Inversion detection, Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) were used to detect the mutation in the proband and his mother. RESULTS: The patient, a 7-year-old boy, was diagnosed with severe HA at 8 months. No inhibitor was developed over 150 exposure days. Intronic inversion detection and Sanger sequencing have failed to identify pathogenic variants, while MLPA revealed a large duplication [Ex 1_22 dup (2 copies)] in the proband, for which his mother was a carrier [Ex 1_22 dup (3 copies)]. Large duplications of the F8 gene have so far been found in 24 HA patients, all of whom had a severe phenotype, only one had a history of inhibitors. CONCLUSION Large duplications of F8 gene are associated with severe HA. The diagnostic rate for HA may be increased by MLPA.
Child ; Factor VIII/genetics* ; Gene Duplication ; Hemophilia A/genetics* ; Humans ; Introns ; Male ; Mutation ; Phenotype

Humans ; Mental Retardation, X-Linked/genetics* ; Methyl-CpG-Binding Protein 2/genetics* ; Gene Duplication

OBJECTIVETo conduct genetic diagnosis for a family in which no exonic deletions and duplications of the dystrophin gene were detected.

METHODSPotential exonic deletions and duplications of the dystrophin gene were initially analyzed with using multiplex ligation-dependent probe amplification (MLPA). Subsequently, all of the 79 exons of the dystrophin gene of the proband and a pregnant woman from the family were analyzed with PCR amplification and DNA sequencing. Following identification of the causative mutation, prenatal diagnosis was provided.

RESULTSMLPA analysis had detected no exonic deletions and duplications of the dystrophin gene. Sequence analysis has identified a C>T mutation on the 22nd nucleotide position of the 70th exon of the dystrophin gene (c.10108 C>T), which has replaced the codon CGA to a stop codon (TGA). The patient's mother and sister were both heterozygous for the same mutation. Upon prenatal diagnosis, the fetus was found to be positive for the Y chromosome sex-determining gene (SRY) and has carried above mutation. The result of short tandem repeat linkage analysis also confirmed that the fetus has inherited the mutant X chromosome.

CONCLUSIONThe causative mutation of the dystrophin gene has been discovered in an affected family, which has enabled prenatal diagnosis of the disease.

Child, Preschool ; Dystrophin ; genetics ; Exons ; Gene Deletion ; Gene Duplication ; Humans ; Male ; Microsatellite Repeats ; Multiplex Polymerase Chain Reaction ; Mutation