The following sample output plots shows

Parents with two children

For SNP data contains 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 show in the following figure. Note that the inheritance differences between the two children can be identified mostly 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 cildren had inherrited the same allele form that parent. Out side of those boxed red MI-S regions, the two siblings had inherrited the opposite allele from that parent. Therefore, in the regions which contain a red MI-S box in both parent's reverse panels, it means that these two children had inherrited the same allele from both parents, referred as "indentical inheritance". On the other hand, a region contains black BPI dots indicates the two children in that reverse pedigree each had inherrited a different allele from that parent. When two children had inherrited the opposite allele for 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 parent had all NoCalls in that region, due to a homozygus deletion.

Parents with three children

With three children, six reverse pedigree panels can be generated: three for the paretnal 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 casue 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 occured in child1's paternal gamete will resulted 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 cross over on her paternal gamete and four on her mathernal gamete (pink arrows). Child Son_2 had one and four (green arrows), while Son_3 had three and three (blow arrows) cross over, on their paternal and maternal gametes, respectively. Note that on the average, maternal gametes have more recombinations than paternal gametes.

Near the lower left corner of the above figure, on the last reverse maternal pedigree panel, there are a pink and a blue arrows 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 indicates there are two events. The reason the last panel did not break that red box into two separate one is due to the close proximity (<3,000,000 bp) plus no BPI dots (which itself was resulted from the red MI-S box on the paternal gamete analysis of that reverse pedigree (fourth panel from the bottom up.) Though such combination is rear, 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, in rare occasion, 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 pedigree of four siblings, each recombination event causes pattern changes in three panels of that parent. Namely, that child plus one of each three other children been treated 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 can not tell exactly which of these two cases is the true cause.

Identification of recombinations on male's chrX

The approach pediSNP used to locate crosover events is to exam all maternal gametes for inheritance differences. Therefore, chromosome X is analized exactly the same way as all other chromosomes. In fact, chromosome X shall be examed 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, form 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 is no crossover event on any of these three sibling's paternal gametes. Namely, no red MI-S boexes, nore bloack BPI dots. The various colored boxes on panel 4 (Rev_S1.S2__Fa) is due to the fact that son #2 was treated as the "mother" in that reverse pedigree. While those boxes are meanningful from SNPtrio's perspective, they are not utilized by pediSNP from identifying meiotic recombination's perspective becuase MI-S and PBI are sufficent for such purpose. The fact that crossovers on Son #1's and Son #2's maternal gametes impacted panels 4 is just the reminfication of current SNP manufactures alway make bi-allelic genotype calls for all SNPs. The parental chomosome Xs in that pedigree are not related to the chomosome X of the child (the Father) of that pedigree. From SNPtrio's perspective, those MI-D, UPI-M and UPI-P boxed indicating the child is not related the the parents, plus, the two regions near p arm and q arm terminals where only MI-D boxes are the regions where both parents have the identical allele.

Results from eight autism families

Show the results of the big table.

loci-of-interest identification

The final pattern consists of

Last updated: April 27, 2009