in sperm-typing data for

Data

Data are presented from 5 donors who are MJD patients of French descent. For details, see the paper.

For donor 1, we have the following data on 156 single sperm typed at both the MJD1 locus and at the closely-linked marker D14S1050, where A represents the mutant MJD1 allele, a represents the wild-type MJD1 allele, B represents the D14S1050 allele linked to the mutant MJD1 allele, and b represents the D14S1050 allele linked the the wild-type MJD1 allele.

Coamplification data (Donor 1)

---- ---b --a- --ab -B-- -B-b -Ba- -Bab A--- A--b A-a- A-ab AB-- AB-b ABa- ABab Total |
12 2 4 67 15 0 1 0 1 1 0 0 50 2 1 0 156 |

For donors 1 through 5, we have the following data on sperm typed at D14S1050, where B represents the allele linked the mutant MJD1 allele while b represents the allele linked to the wild-type MJD1 allele.

Donor 1

---- ---b -B-- -B-b Total |
19 92 95 0 206 |

Donor 2

---- ---b -B-- -B-b Total |
40 90 91 0 221 |

Donor 3

---- ---b -B-- -B-b Total |
15 87 91 0 193 |

Donor 4

---- ---b -B-- -B-b Total |
29 104 98 4 235 |

Donor 5

---- ---b -B-- -B-b Total |
9 79 83 0 171 |

Model

We performed a likelihood-based analysis of segregation distortion in the single sperm data using the SPERMSEG program of McPeek (1999) "SPERMSEG: analysis of segregation distortion in sigle-sperm data" American Journal of Human Genetics 65:1195-1197. The specific model fit to these data assumed

Parameter Estimates (with 95% confidence intervals)

Parameter s d1(12) d1(11) d1(2) d1(3) d1(4) d1(5) d2 am(A) am(B) am(a) am(b) c(A) c(B) c(a) c(b) |
Estimate 0.496009 0.923240 0.940795 0.847629 0.956031 0.908047 0.982358 0.000000 0.777733 0.981824 0.974617 0.946011 0.000000 0.000000 0.018374 0.011326 |
Lower Limit .461 |
Upper Limit .531 |

Details of the Analysis

A Monte Carlo goodness-of-fit test using SPERMSEG did not indicate misfit of this model to the data (p-value .3). A likelihood-ratio chi-square test comparing the above model to the model in which the segregation parameter is set equal to 1/2 does not indicate significant segregation distortion (p-value .82). Significant inter-experimental variability showed up in the parameter representing probability of 1 sperm deposited (d1). A Monte Carlo goodness-of-fit test of the model in which all d1 parameters were equal showed significant misfit (simulated p-value < .05). The mutant MJD1 allele showed reduced amplification, as is sometimes the case with large repeats, which could potentially result in a biased estimate of segregation probability and hide any segregation distortion in favor of that allele. However, the amplification rates of the two alleles of the linked marker were very close, with the amplification rate for the allele linked to the mutant MJD1 allele actually being slightly higher (not significantly different p-value .29). Thus, using the linked marker, we do not expect the estimate of segregation distortion to be biased, particularly not in the direction of hiding segregation distortion in favor the the mutant MJD1. We do not detect such segregation distortion in these data.