METHODS FOR ALLELE CALLING AND PLOIDY CALLING
Disclosed herein is a system and method for making allele calls, and for determining the ploidy state, in one or a small set of cells, or where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed and the haplotypes are determined using expected similarities between the target genome and the knowledge of the genomes of genetically related individuals. In one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the genetic data from both parents, and possibly one or more sperm and/or sibling embryos. In another embodiment, the chromosome copy number can be determined using the same input data. In another embodiment, these determinations are made for embryo selection during IVF, for non-invasive prenatal diagnosis, or for making phenotypic predictions.
1 - 20 . (canceled)
21 . A method for determining an allelic state in a set of alleles, in a target individual, and from one or both parents of the target individual, and optionally from one or more related individuals, the method comprising:
obtaining genetic data from the target individual, and from the one or both parents, and from any related individuals;
creating a set of at least one allelic hypothesis for the target individual, and for the one or both parents, and optionally for the one or more related individuals, where the hypotheses describe possible allelic states in the set of alleles;
determining a statistical probability for each allelic hypothesis in the set of hypotheses given the obtained genetic data; and
determining the allelic state for each of the alleles in the set of alleles for the target individual, and for the one or both parents, and optionally for the one or more related individuals, based on the statistical probabilities of each of the allelic hypotheses.
22 . The method of claim 1 , wherein the related individuals are siblings of the target individual.
23 . The method of claim 1 , wherein the allelic state determination is performed in the context of in vitro fertilization, and where the target individual is an embryo.
24 . The method of claim 1 , wherein the allelic state determination is performed in the context of non-invasive prenatal diagnosis, and where the target individual is a fetus.
25 . The method of claim 1 , wherein determining the allelic state for each of the alleles in the set of alleles in the target individual comprises determining a phased genotype at a set of alleles for the target individual.
26 . The method of claim 1 , wherein the genetic data comprise single nucleotide polymorphisms measured by genotyping array and/or DNA sequencing, and wherein the genetic data comprise at least 22 chromosomes of at least 1,000 SNPs each.
27 . The method of claim 1 , wherein the method comprises using platform response models to determine a characteristic measurement bias of a genotyping technique.
28 . The method of claim 1 , wherein the method takes into account a possibility of DNA crossovers that may occur during meiosis.
29 . The method of claim 1 , wherein the target individual is an embryo, and wherein determining the allelic state in the set of alleles of the target individual is performed to select at least one embryo for transfer in the context of WF, and where the related individuals are selected from the group consisting of one or more embryos that are from the same parents, one or more sperm from the father, and combinations thereof.
30 . The method of claim 1 , wherein the method is performed alongside or in conjunction with a method that determines a number of copies of a given chromosome segment present in the target individual, and where both methods use a same cell, or group of cells, from the target individual as a source of genetic data.