Sample Output

The following sample output plots shows

Parents with two children

Parents with three children

Parents with four children

Identification of recombinations on male's chrX

Results from eight autism families

Loci-of-interest identification


Parents with two children

For SNP data including two parents and two children, pediSNP will generate two panels for the normal trios (father + mother -> child) and two reverse trios (child1 + child2 -> parent), as shown in the following figure. Note that the inheritance differences between the two children can be classified into three types: identical inheritance, semi-identical inheritance, and opposite inheritance, shown as boxed regions in the following figure.

In reverse pedigree panels, regions containing a red MI-S box indicate the two children had inherited the same allele from that parent. Outside of those boxed red MI-S regions, the two siblings had inherited the opposite allele from that parent. Therefore, in the regions which contain a red MI-S box in both parents' reverse panels, it means that these two children had inherited the same allele from both parents, referred to as "identical inheritance". On the other hand, a region contains black BPI dots indicates the two children in that reverse pedigree each had inherited a different allele from that parent. When two children had inhrrited the opposite allele from both parents, both parents' reverse panels contain only black BPI dots, without any red MI-S boxes. Single black BPI dot, single red MI-S dot and all other colored dots or boxes are not informative for the purpose of inheritance differences identification. When all four panels are blank, it means either the parents share one allele (Identity-By-State=1), or one of the parents had all NoCalls in that region, due to a homozygous deletion.

Image chr3 of two kids



Parents with three children

With three children, six reverse pedigree panels can be generated: three for the paternal gametes and three for the maternal gametes. With three gametes per parent, we can identify which gamete had a recombination event. A recombination event in one child's gamete will cause changes of inheritance pattern in all the reverse pedigree panels which contain that child as one of the parents. With three children, say child1, child2 and child3, a recombination event which occurred in child1's paternal gamete will result in a change in the child1+child2->father panel and the child1+child3->father panel. For example, child Daughter_1 of the following figure had two crossovers on her paternal gamete and four on her maternal gamete (pink arrows). Child Son_2 had one and four (green arrows), while Son_3 had three and three (blue arrows) crossovers, on their paternal and maternal gametes, respectively. Note that on the average, maternal gametes have more recombinations than paternal gametes.

Image chr2 of three kinds

Near the lower left corner of the above figure, on the last reverse maternal pedigree panel, there are a pink and a blue arrow pointing to the middle of a red MI-S box. From the other end of these two colored lines, there are clearly two matching edges of two recombination events. The extra black BPI dots next to the blue line (compared with those next to the pink line) also indicate there are two events. The reason the last panel did not break that red box into two separate ones is due to the close proximity (less than 3,000,000 bp) and the absence of BPI dots (which was a result of the red MI-S box on the paternal gamete analysis of that reverse pedigree, fourth panel from the bottom.) Though such combinations are rare, they can always be identified as shown here.


Parents with four children

Most mammalian meiotic recombinations occur in recombination hot spots. There are many recombination hot spots on each chromosome. With two siblings, we can tell from the inheritance patterns that there was a recombination, without sufficient information to tell which child had it. With four siblings, on rare occasions, like indicated by the thick black arrow in the middle of the following figure, we will find two overlapping recombination sites.

We know two recombination events had happened almost at the same site (below the resolution of informative SNPs). Note that for a pedigree of four siblings, each recombination event causes pattern changes in three panels of that parent. Namely, the recombinant child plus one of each of the three other children being analyzed as parents in those reverse pedigrees. At the overlapping site, note that four, not three, nor five, out of the six paternal panels have a pattern change. In this case, it could either be caused by a recombination for both daughter_1 and son_2, or caused by a recombination for both son_3 and daughter_4. We cannot tell exactly which of these two cases is the true cause.

Image chr1 of four kids



Identification of recombinations on male's chrX

The approach pediSNP uses to locate crossover events is to examine all maternal gametes for inheritance differences. Therefore, chromosome X is analyzed exactly the same way as all other chromosomes. In fact, chromosome X shall be examined exactly the same way by all methods intended for locating meiotic recombination events. Because, upon the completion of meiotic recombination, the future sex of the oocyte is still yet to be determined. In the following figure, from maternal gametes, pediSNP identified one crossover event for son #1, one for son #2, and three events for daughter #3. In addition, pediSNP also identified that there was no crossover events on any of these three sibling's paternal gametes. Namely, no red MI-S boxes, nor black BPI dots. The various colored boxes on panel 4 (Rev_S1.S2__Fa) are due to the fact that son #2 was treated as the "mother" in that reverse pedigree. While those boxes are meaningful from SNPtrio's perspective, they are not utilized by pediSNP for identification of meiotic recombination, because MI-S and PBI are sufficient for this purpose. The fact that crossovers on Son #1's and Son #2's maternal gametes impacted panels 4 is just the ramification of that fact that currently SNP software makes bi-allelic genotype calls for all SNPs. The parental chromosome X's in that pedigree are not related to the chromosome X of the child (the Father) of that pedigree. From SNPtrio's perspective, those MI-D, UPI-M and UPI-P boxes indicate the child is not related to the parents, plus, the two regions near the p and q arm terminals, with only MI-D boxes, are the regions where both parents have the identical allele.

Image chrX of three kinds



Results from eight autism families

Show the results of the big table. UNDER CONSTRUCTION.

Image results from 8 autism families



Loci-of-interest identification

UNDER CONSTRUCTION.

Image chr3 of AU1043