Fetal aneuploidy detection by sequencing
First Claim
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1. A method for determining a ratio of signal intensities of amplification products for a maternal allele in a first genomic region on a first chromosome suspected of being aneuploid and for a maternal allele in a second genomic region on a second chromosome that is not aneuploid or not suspected of being aneuploid in a maternal blood sample, the method comprising:
- a. enriching a maternal blood sample for fetal genomic DNA to produce an enriched sample comprising fetal and maternal genomic DNA (gDNA) having an increased concentration of fetal gDNA relative to before enrichment;
b. hybridizing probes to each of a plurality of loci in the gDNA on at least two different chromosomes;
c. ligating the hybridized probes at each locus to each other to create an amplification template specific to each locus;
d. amplifying the amplification template specific to each locus to create amplification products;
e. hybridizing the amplification products to probes on a microarray; and
f. detecting, among the amplification products hybridized to probes on the microarray, a signal intensity of the amplification products for a maternal allele in a first genomic region on a first chromosome suspected of being aneuploid and a signal intensity of the amplification products for a maternal allele in a second genomic region on a second chromosome that is not aneuploid or not suspected of being aneuploid, and determining a ratio of the signal intensity of the amplification products for the maternal allele in the first genomic region to the signal intensity of the amplification products for the maternal allele in the second genomic region.
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Abstract
The present invention provides apparatus and methods for enriching components or cells from a sample and conducting genetic analysis, such as SNP genotyping to provide diagnostic results for fetal disorders or conditions.
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11 Claims
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1. A method for determining a ratio of signal intensities of amplification products for a maternal allele in a first genomic region on a first chromosome suspected of being aneuploid and for a maternal allele in a second genomic region on a second chromosome that is not aneuploid or not suspected of being aneuploid in a maternal blood sample, the method comprising:
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a. enriching a maternal blood sample for fetal genomic DNA to produce an enriched sample comprising fetal and maternal genomic DNA (gDNA) having an increased concentration of fetal gDNA relative to before enrichment; b. hybridizing probes to each of a plurality of loci in the gDNA on at least two different chromosomes; c. ligating the hybridized probes at each locus to each other to create an amplification template specific to each locus; d. amplifying the amplification template specific to each locus to create amplification products; e. hybridizing the amplification products to probes on a microarray; and f. detecting, among the amplification products hybridized to probes on the microarray, a signal intensity of the amplification products for a maternal allele in a first genomic region on a first chromosome suspected of being aneuploid and a signal intensity of the amplification products for a maternal allele in a second genomic region on a second chromosome that is not aneuploid or not suspected of being aneuploid, and determining a ratio of the signal intensity of the amplification products for the maternal allele in the first genomic region to the signal intensity of the amplification products for the maternal allele in the second genomic region. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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Specification