Evidence of a Large-Scale Functional Organization of Mammalian Chromosomes: Authors' Reply

Sagiv Shifman,Jordana Tzenova Bell,Robert W Williams,Martin S Taylor,Richard Mott,Richard R Copley,Jonathan Flint

doi:10.1371/journal.pbio.0050128

Abstract

We agree with Petkov and colleagues that including the BXD lines (“new BXD”), which were derived from advanced intercross lines (AIL), increases the map length in the recombinant inbred (RI) lines. As we note in our paper “One BXD subset was developed using advanced intercross populations and therefore contains approximately 1.7 times more recombinants per line”[1]. If the “new BXD” set were analyzed by itself, an AIL-specific map expansion factor should be applied [2]. However since our motivation was to obtain an accurate estimation of the relative rates of recombination in different regions of the genome, we analyzed all of the RIs together to increase the number of recombination events and the overall density of polymorphic markers. This increased our sensitivity, for example, to identify regions of extremely low and high recombination rates. There are a number of explanations as to why the map length should differ from that expected on the basis of the Haldane-Waddington equation [3,4]. The estimated map distance of the RIs depends also on the marker density [2] and on the number of inbred generations [5], factors that act to reduce the map length relative to the Haldane-Waddington theoretical equation (which assumes a fully inbred line). It has been hypothesized that “the apparent genetic interference of the accumulated generations (e.g., RIs) differs from the genetic interference acting in each meiosis and that commonly used map functions lead to reduced map distance estimates in the advanced designs” [5]. Consequently, it is not clear that the observed can be explained solely in the way suggested by Petkov et al.

Highlights

The failure of Shifman et al to confirm this latter observation derived from their inclusion of the so-called “new BXD” lines in Table 3 of their paper that served as the basis for calculating the genetic length of recombinant inbred lines
Applying the Haldane-Waddington equation to these mice for calculating genetic distances is not appropriate, because they were developed from an advanced intercross population with a resulting excess of recombinations
Shifman et al have generously made their initial data available to us; using a revised Table 3 with these lines removed and the same methodology as Shifman et al generates a map length of 1393 ± 14 cM. This is 14.7% shorter than their estimate of 1630 cM for single meiosis genetic length of the mouse genome; we reported a reduction of 18.1% using different data sets and methodologies

Summary

Introduction

The failure of Shifman et al to confirm this latter observation derived from their inclusion of the so-called “new BXD” lines in Table 3 of their paper that served as the basis for calculating the genetic length of recombinant inbred lines.

Results

Conclusion