Roche Molecular Systems, Inc.

Hoffmann-la Roche Inc.

Cetus Corporation

Children's Hospital Research Center at Oakland

Conexio Genomics Pty Ltd

The Scripps Research Institute

Roche Diagnostics Gmbh

F. Hoffmann-la Roche Ag

Henry A Erlich

Glenn T Horn

Randall K Saiki

Kary B Mullis

David H Gelfand

Teodorica L Bugawan

Stephen J Scharf

Janelle A Noble

Norman Arnheim

Elizabeth A Trachtenberg

Damian Goodridge

Lloyd Gordon Bentley

Ann B Begovich

Martha Ladner

Raymond J Apple

Nancy J Schoenbrunner

Russell G Higuchi

Ann Begovich

Gary A Peltz

Alison Tsan

Daniel R Salomon

Shirley Y Kwok

John J Sninsky

Cherie Holcomb

Rebecca Lynne Reynolds

Andrew Grupe

David H Mack

Nick Newton

Bryan Hoglund

Robert L Griffith

Gabriele Zangenberg

Ulf B Gyllensten

Karen Myra Walker

Ann Maria Valdes

Daniel B Mirel

Melinda Rastrou

Priscilla Moonsamy

Gordon Bentley

Elizabeth Trachtenberg

Disclosed is a method of determining KIR genotypes for one or more individuals in parallel, the method comprising: for each individual, amplifying the polymorphic exon sequences of the KIR genes, pooling the KIR amplicons, performing emulsion PCR followed by pyrosequencing in parallel to determine all the amplicon sequences present in the individual to determine which KIR alleles are present in the individual.

Determination of KIR haplotypes associated with disease

The invention is a method of detecting or assessing solid organ graft (transplant) rejection by detecting donor-specific HLA alleles in a blood sample of a graft (transplant) recipient. The invention further comprises a method of detecting the presence of maternal cells in a blood sample of an offspring.

Non-invasive early detection of solid organ transplant rejection by quantitative analysis of mixtures by deep sequencing of HLA gene amplicons using next generation systems

The present invention provides methods and reagents for determining sequence variants present at the IL4 receptor, IL-4 and IL-13 loci, which facilitate identifying individuals at risk for type 1 diabetes.

Association of polymorphisms in IL4-related genes with autoimmune disease

Methods and reagents for determining sequence variants present at the TCF-1 locus, which facilitates identifying individuals at risk for Th1 diseases, such as type 1 diabetes or multiple sclerosis, or Th2 diseases, such as allergic asthma or atopy.

TCF-1 nucleotide sequence variation

The present invention is directed to a process for amplifying any target nucleic acid sequence contained in a nucleic acid or mixture thereof using a thermostable enzyme. The process comprises treating separate complementary strands of the nucleic acid with a molar excess of two oligonucleotide primers, extending the primers with a thermostable enzyme to form complementary primer extension products which act as templates for synthesizing the desired nucleic acid sequence, and detecting the sequence so amplified. The steps of the reaction can be repeated as often as desired and involve temperature cycling to effect hybridization, promotion of activity of the enzyme, and denaturation of the hybrids formed.

Kits for amplifying and detecting nucleic acid sequences

DNA sequences and corresponding amino acid sequences from the HLA class II beta region of the human genome that are associated with insulin-dependent diabetes mellitus (IDDM) and,(PV) have been identified. Specifically, marker DNA sequences which detect either directly or indirectly the identity of the codon encoding for the amino acid at position 57 of the DQ&bgr; protein sequence are disclosed as well as sequences from the DR&bgr; region. These sequences may be used to generate DNA hybridization probes and antibodies for assays to detect a person's susceptibility to autoimmune diseases, such as IDDM and PV. Such antibodies and peptides encoded by said DNA sequences can be used therapeutically or prophylactically.

Characterization and detection of sequences associated with autoimmune diseases

Kits for amplifying and detecting nucleic acid sequences, including a

DNA sequences and corresponding amino acid sequences from the HLA class II beta region of the human genome that are associated with insulin-dependent diabetes mellitus (IDDM) and Pemphigus vulgaris (PV) have been identified. Specifically, marker DNA sequences which detect either directly or indirectly the identity of the codon encoding for the amino acid at position 57 of the DQ.beta. protein sequence are disclosed as well as sequences from the DR.beta. region. These sequences may be used to generate DNA hybridization probes and antibodies for assays to detect a person's susceptibility to autoimmune diseases, such as IDDM and PV. Such antibodies and peptides encoded by said DNA sequences can be used therapeutically or prophylactically.

Characterization and detection of sequences associated with autoimmune

Single or multiple nucleotide variations in nucleic acid sequence can be detected in nucleic acids by a process whereby the sample suspected of containing the relevant nucleic acid is repeatedly treated with primers, nucleotide triphosphates, and an agent for polymerization of the triphosphates and then denatured, in a process which amplifies the sequence containing the nucleotide variation if it is present. In one embodiment, the sample is spotted on a membrane and treated with a labeled sequence-specific oligonucleotide probe. Hybridization of the probe to the sample is detected by the label on the probe.

Process for detecting specific nucleotide variations and genetic

Methods and reagents for HLA DRbeta DNA typing

A process for determining the genotype of an individual with respect to the alleles at the HLA DP locus involves obtaining a sample of nucleic acid from the individual, and hybridizing the nucleic acids with a panel of probes specific for variant segments of DPalpha and DPbeta genes. Because the variation between DPbeta alleles is highly dispersed throughout the second exon of the DPbeta gene, the discovery of many different DPbeta alleles makes the process far more discriminating and informative than cellular, RFLP, or serological methods. The process can also be carried out on amplified nucleic acid produced by the polymerase chain reaction using primers specific for the second exon of the DPalpha and DPbeta genes. HLA DP DNA typing methods are useful in the prevention of graft rejection and host versus graft disease, in determining susceptibility to autoimmune diseases, in providing evidence concerning the derivation from an individual of forensic samples, and in paternity testing.

Method for HLA DP typing

Primers for amplification of specific nucleic acid sequences of the second and third exon of HLA Class I A gene and probes for identifying polymorphic sequences contained in the amplified DNA can be used in processes for typing homozygous or heterozygous samples from a variety of sources and for detecting allelic variants not distinguishable by serological methods. This HLA-A DNA typing system can be used in a forward or reverse dot-blot format that is simple and rapid to perform, produces detectable signals in minutes, and can be used for tissue typing, determining individual identity, and identifying disease susceptible individuals.

Methods and reagents for HLA class I A locus DNA typing

Growing community of inventors

Oakland, CA, United States of America

Henry A Erlich