US 12,065,704 B2
Diagnosing fetal chromosomal aneuploidy using massively parallel genomic sequencing
Yuk-Ming Dennis Lo, Kowloon (HK); Rossa Wai Kwun Chiu, New Territories (HK); and Kwan Chee Chan, Kowloon (HK)
Assigned to The Chinese University of Hong Kong, New Territories (HK)
Filed by Yuk-Ming Dennis Lo, Kowloon (HK); Rossa Wai Kwun Chiu, New Territories (HK); and Kwan Chee Chan, Kowloon (HK)
Filed on Mar. 23, 2011, as Appl. No. 13/070,251.
Application 13/070,251 is a continuation of application No. 12/614,350, filed on Nov. 6, 2009.
Application 12/614,350 is a continuation in part of application No. 12/178,181, filed on Jul. 23, 2008.
Claims priority of provisional application 60/951,438, filed on Jul. 23, 2007.
Prior Publication US 2012/0003636 A1, Jan. 5, 2012
Int. Cl. C12Q 1/6886 (2018.01); C12Q 1/6809 (2018.01); C12Q 1/6827 (2018.01); C12Q 1/6874 (2018.01); C12Q 1/6883 (2018.01); G16B 20/00 (2019.01); G16B 20/10 (2019.01); G16B 20/20 (2019.01); G16B 30/00 (2019.01); G16B 30/10 (2019.01)
CPC C12Q 1/6886 (2013.01) [C12Q 1/6809 (2013.01); C12Q 1/6827 (2013.01); C12Q 1/6874 (2013.01); C12Q 1/6883 (2013.01); G16B 20/00 (2019.02); G16B 20/10 (2019.02); G16B 20/20 (2019.02); G16B 30/00 (2019.02); G16B 30/10 (2019.02); C12Q 2600/156 (2013.01)] 20 Claims
 
1. A method for identifying a fetal aneuploidy in a maternal biological sample that includes cell-free fetal DNA fragments from the genome of a fetus and cell-free maternal DNA fragments from the genome of the mother of the fetus, the method comprising:
performing a random sequencing of cell-free DNA fragments from the maternal biological sample to obtain sequenced tags for cell-free maternal DNA fragments from the genome of the mother and for cell-free DNA fragments from the genome of the fetus;
determining for each of a plurality of sequences tags to be aligned the length of the portion of the DNA fragment that corresponds to the sequenced tag and the identity of the sequence information at both ends of the sequenced tag;
aligning the sequenced tags to a reference human genome based on the determined length and the determined identity of the sequence information at both ends of the sequenced tag, to identify the chromosomes from which the sequenced tags originate;
determining i) a first number of sequenced tags of at least one first chromosome based on sequenced tags originating from the at least one first chromosome, and ii) a second number of sequenced tags of a second chromosome based on sequenced tags originating from the second chromosome; and
comparing the first number to the second number to determine whether a fetal aneuploidy exists for the second chromosome.