The Experts below are selected from a list of 474 Experts worldwide ranked by ideXlab platform

Coller B S - One of the best experts on this subject based on the ideXlab platform.

  • The molecular genetic basis of Glanzmann thrombasthenia in the Iraqi-Jewish and Arab populations in Israel.
    1991
    Co-Authors: Newman P J, Seligsohn U, Lyman S, Coller B S
    Abstract:

    Glanzmann thrombasthenia is an autosomal recessive bleeding disorder characterized by a decrease or absence of functional platelet glycoprotein (GP) IIb-IIIa (alpha IIb beta 3) integrin receptors. Although thrombasthenia is a rare disorder, its occurrence is increased in some regions of the world where intracommunity marriage and consanguinity are commonplace, resulting in increased expression of autosomal recessive traits. We have been studying two populations having an unusually high frequency of Glanzmann Disease, Iraqi Jews and Arabs living in Israel, and were able to distinguish the populations on the basis of immunodetectable GPIIIa and platelet surface vitronectin receptor (alpha v beta 3) expression. In this article, we describe molecular genetic studies based on use of the PCR that have allowed us to characterize platelet mRNA sequences encoding GPIIb and GPIIIa from patients in these populations. In six of six Iraqi-Jewish families studied, cDNA sequence analysis identified an 11-base deletion within exon 12 of the GPIIIa gene. This mutation produces a frameshift leading to protein termination shortly before the transmembrane domain of GPIIIa. In contrast, a 13-base deletion encompassing the splice acceptor site of exon 4 of the GPIIb gene was found in three of five Arab kindreds studied. This deletion results in forced alternative splicing to a downstream AG acceptor, producing a 6-amino acid deletion in the GPIIb protein, including a single cysteine residue. These nucleotide sequence variations were exploited to design a rapid, PCR-based oligonucleotide dot-blot hybridization test for both pre- and postnatal diagnosis of Glanzmann Disease. These studies demonstrate the heterogeneity of Glanzmann thrombasthenia in different populations, and its homogeneity within geographically restricted populations, and offer insight into the requirements for integrin surface expression

Newman P J - One of the best experts on this subject based on the ideXlab platform.

  • The molecular genetic basis of Glanzmann thrombasthenia in the Iraqi-Jewish and Arab populations in Israel.
    1991
    Co-Authors: Newman P J, Seligsohn U, Lyman S, Coller B S
    Abstract:

    Glanzmann thrombasthenia is an autosomal recessive bleeding disorder characterized by a decrease or absence of functional platelet glycoprotein (GP) IIb-IIIa (alpha IIb beta 3) integrin receptors. Although thrombasthenia is a rare disorder, its occurrence is increased in some regions of the world where intracommunity marriage and consanguinity are commonplace, resulting in increased expression of autosomal recessive traits. We have been studying two populations having an unusually high frequency of Glanzmann Disease, Iraqi Jews and Arabs living in Israel, and were able to distinguish the populations on the basis of immunodetectable GPIIIa and platelet surface vitronectin receptor (alpha v beta 3) expression. In this article, we describe molecular genetic studies based on use of the PCR that have allowed us to characterize platelet mRNA sequences encoding GPIIb and GPIIIa from patients in these populations. In six of six Iraqi-Jewish families studied, cDNA sequence analysis identified an 11-base deletion within exon 12 of the GPIIIa gene. This mutation produces a frameshift leading to protein termination shortly before the transmembrane domain of GPIIIa. In contrast, a 13-base deletion encompassing the splice acceptor site of exon 4 of the GPIIb gene was found in three of five Arab kindreds studied. This deletion results in forced alternative splicing to a downstream AG acceptor, producing a 6-amino acid deletion in the GPIIb protein, including a single cysteine residue. These nucleotide sequence variations were exploited to design a rapid, PCR-based oligonucleotide dot-blot hybridization test for both pre- and postnatal diagnosis of Glanzmann Disease. These studies demonstrate the heterogeneity of Glanzmann thrombasthenia in different populations, and its homogeneity within geographically restricted populations, and offer insight into the requirements for integrin surface expression

Seligsohn U - One of the best experts on this subject based on the ideXlab platform.

  • The molecular genetic basis of Glanzmann thrombasthenia in the Iraqi-Jewish and Arab populations in Israel.
    1991
    Co-Authors: Newman P J, Seligsohn U, Lyman S, Coller B S
    Abstract:

    Glanzmann thrombasthenia is an autosomal recessive bleeding disorder characterized by a decrease or absence of functional platelet glycoprotein (GP) IIb-IIIa (alpha IIb beta 3) integrin receptors. Although thrombasthenia is a rare disorder, its occurrence is increased in some regions of the world where intracommunity marriage and consanguinity are commonplace, resulting in increased expression of autosomal recessive traits. We have been studying two populations having an unusually high frequency of Glanzmann Disease, Iraqi Jews and Arabs living in Israel, and were able to distinguish the populations on the basis of immunodetectable GPIIIa and platelet surface vitronectin receptor (alpha v beta 3) expression. In this article, we describe molecular genetic studies based on use of the PCR that have allowed us to characterize platelet mRNA sequences encoding GPIIb and GPIIIa from patients in these populations. In six of six Iraqi-Jewish families studied, cDNA sequence analysis identified an 11-base deletion within exon 12 of the GPIIIa gene. This mutation produces a frameshift leading to protein termination shortly before the transmembrane domain of GPIIIa. In contrast, a 13-base deletion encompassing the splice acceptor site of exon 4 of the GPIIb gene was found in three of five Arab kindreds studied. This deletion results in forced alternative splicing to a downstream AG acceptor, producing a 6-amino acid deletion in the GPIIb protein, including a single cysteine residue. These nucleotide sequence variations were exploited to design a rapid, PCR-based oligonucleotide dot-blot hybridization test for both pre- and postnatal diagnosis of Glanzmann Disease. These studies demonstrate the heterogeneity of Glanzmann thrombasthenia in different populations, and its homogeneity within geographically restricted populations, and offer insight into the requirements for integrin surface expression

Lyman S - One of the best experts on this subject based on the ideXlab platform.

  • The molecular genetic basis of Glanzmann thrombasthenia in the Iraqi-Jewish and Arab populations in Israel.
    1991
    Co-Authors: Newman P J, Seligsohn U, Lyman S, Coller B S
    Abstract:

    Glanzmann thrombasthenia is an autosomal recessive bleeding disorder characterized by a decrease or absence of functional platelet glycoprotein (GP) IIb-IIIa (alpha IIb beta 3) integrin receptors. Although thrombasthenia is a rare disorder, its occurrence is increased in some regions of the world where intracommunity marriage and consanguinity are commonplace, resulting in increased expression of autosomal recessive traits. We have been studying two populations having an unusually high frequency of Glanzmann Disease, Iraqi Jews and Arabs living in Israel, and were able to distinguish the populations on the basis of immunodetectable GPIIIa and platelet surface vitronectin receptor (alpha v beta 3) expression. In this article, we describe molecular genetic studies based on use of the PCR that have allowed us to characterize platelet mRNA sequences encoding GPIIb and GPIIIa from patients in these populations. In six of six Iraqi-Jewish families studied, cDNA sequence analysis identified an 11-base deletion within exon 12 of the GPIIIa gene. This mutation produces a frameshift leading to protein termination shortly before the transmembrane domain of GPIIIa. In contrast, a 13-base deletion encompassing the splice acceptor site of exon 4 of the GPIIb gene was found in three of five Arab kindreds studied. This deletion results in forced alternative splicing to a downstream AG acceptor, producing a 6-amino acid deletion in the GPIIb protein, including a single cysteine residue. These nucleotide sequence variations were exploited to design a rapid, PCR-based oligonucleotide dot-blot hybridization test for both pre- and postnatal diagnosis of Glanzmann Disease. These studies demonstrate the heterogeneity of Glanzmann thrombasthenia in different populations, and its homogeneity within geographically restricted populations, and offer insight into the requirements for integrin surface expression

C.p.m. Hayward - One of the best experts on this subject based on the ideXlab platform.

  • Genomic approaches to bleeding disorders
    'Wiley', 2016
    Co-Authors: F. Peyvandi, C.p.m. Hayward
    Abstract:

    The genes encoding the coagulation factors were characterized over two decades ago. Since then, significant progress has been made in the genetic diagnosis of the two commonest severe inherited bleeding disorders, haemophilia A and B. Experience with the genetic of inherited rare bleeding disorders and platelet disorders is less well advanced. Rare bleeding disorders are usually inherited as autosomal recessive disorders, while it is now clear that a number of the more common platelet function disorders are inherited as autosomal dominant traits. In both cases, DNA sequencing has been useful since most of these disorders are due to mutations located at the coding regions or splice sites of genes encoding the abnormal protein. However, in 5-10% of patients affected with severe clotting factor deficiencies, no genetic defect can be identified and until recently, the genetic characterization of inherited platelet disorders had been confined to the more prevalent conditions such as Glanzmann Disease and Bernard-Soulier syndrome. In patients with no gene mutations identified, so far, the role of next-generation sequencing as well as of other new genomic technologies will very likely have increasing importance. However, such methods require extensive bioinformatics analysis that, in turn will require critical revision of our current diagnostic infrastructure