A method of testing for an abnormal distribution of a specified chromosome portion in a sample obtained from a subject, wherein the sample is a mixture of fetal and maternal DNA in a maternal plasma sample, comprising: (a) obtaining sequences from multiple chromosome portions of the mixed sample by massively parallel sequencing to obtain a number of sequence tags of sufficient length of determined sequence to be assigned to a chromosome location within a human reference genome; (b) assigning the sequence tags to corresponding chromosome portions including at least one normally distributed chromosome portion and the specified chromosome portion, by comparing the sequences of the tags to a human reference genomic sequence and assigning the sequence tags to a certain chromosome and to a certain position along the chromosome; (c) determining values for numbers of sequence tags mapping to chromosome portions by using a number of windows of defined length within the at least one normally distributed chromosome portion to obtain a first value from the number of sequence tags mapped to the at least one normally distributed chromosome portion and within the specified chromosome portion to obtain a second value from the number of sequence tags mapped to the specified chromosome portion, wherein the first value and the second value are calculated using the windows to account for intra-chromosomal and inter-chromosomal variation in the distribution of the sequence tags; and (d) using the values from step (c) to determine a differential, between the first value and the second value, which is determinative of the over-representation or under-representation of the specified chromosome portion in the mixture of maternal and fetal DNA,wherein the method further includes correcting for GC bias of the sequence reads from the massively parallel sequencing, by: (i) dividing the human reference genome into a number of windows of defined length within each chromosome and calculating the GC content of each window; (ii) calculating the relationship between sequence coverage and GC content of each window by determining a number of reads per a given window and a GC content of that window; and (ii) assigning a weight to said number of reads per a given window based on GC content, where the weight has a relationship to GC content such that increasing numbers of reads with increasing GC content results in decreasing weight per increasing GC content. (a) obtaining sequences from multiple chromosome portions of the mixed sample by massively parallel sequencing to obtain a number of sequence tags of sufficient length of determined sequence to be assigned to a chromosome location within a human reference genome; (b) assigning the sequence tags to corresponding chromosome portions including at least one normally distributed chromosome portion and the specified chromosome portion, by comparing the sequences of the tags to a human reference genomic sequence and assigning the sequence tags to a certain chromosome and to a certain position along the chromosome; (c) determining values for numbers of sequence tags mapping to chromosome portions by using a number of windows of defined length within the at least one normally distributed chromosome portion to obtain a first value from the number of sequence tags mapped to the at least one normally distributed chromosome portion and within the specified chromosome portion to obtain a second value from the number of sequence tags mapped to the specified chromosome portion, wherein the first value and the second value are calculated using the windows to account for intra-chromosomal and inter-chromosomal variation in the distribution of the sequence tags; and (d) using the values from step (c) to determine a differential, between the first value and the second value, which is determinative of the over-representation or under-representation of the specified chromosome portion in the mixture of maternal and fetal DNA,wherein the method further includes correcting for GC bias of the sequence reads from the massively parallel sequencing, by: (i) dividing the human reference genome into a number of windows of defined length within each chromosome and calculating the GC content of each window; (ii) calculating the relationship between sequence coverage and GC content of each window by determining a number of reads per a given window and a GC content of that window; and (ii) assigning a weight to said number of reads per a given window based on GC content, where the weight has a relationship to GC content such that increasing numbers of reads with increasing GC content results in decreasing weight per increasing GC content. (i) dividing the human reference genome into a number of windows of defined length within each chromosome and calculating the GC content of each window; (ii) calculating the relationship between sequence coverage and GC content of each window by determining a number of reads per a given window and a GC content of that window; and (ii) assigning a weight to said number of reads per a given window based on GC content, where the weight has a relationship to GC content such that increasing numbers of reads with increasing GC content results in decreasing weight per increasing GC content.