The affected-pedigree-member (APM) method of linkage analysis is a nonparametric statistic for testing for nonindependent segregation of a marker to affected members of a pedigree. We present here results of a simulation study evaluating the power of the APM method to detect linkage. We have systematically explored, by computer simulation, the effect of a variety of factors on the power to detect linkage using the single-locus APM statistic. These factors include mode of inheritance, marker polymorphism, the distance between marker and disease, phenocopy rate, heterogeneity, and misspecified marker allele frequencies. We also evaluated the relative power obtained under fixed-structure sampling and sequential sampling. For a dominant disease, sequential sampling led to increased power as compared to fixed-structure sampling, while for a recessive disease, there was no clear advantage in sampling beyond nuclear families.

The objective of this study was to determine the relative risk for aneuploidy in the presence of a cardiac intraventricular echogenic focus in a patient population at high risk for aneuploidy. A retrospective cohort study was conducted on patients referred to a fetal diagnostic center who were undergoing amniocentesis. Records and second trimester sonograms were reviewed. Approximately 5100 comprehensive prenatal sonograms were obtained over a 2 year study period. Karyotyping by amniocentesis was done in 2412 women; 84 of the karyotypes (3.5%) were abnormal. Fetuses with no ultrasonographic findings suggestive of aneuploidy had a 1.4% (28 of 1940) prevalence of significant chromosomal abnormalities. An intraventricular echogenic focus was found in 149 of the women with karyotype analysis; 15 had an abnormal karyotype. Fetuses with intraventricular echogenic foci had a relative risk of 3.30 of aneuploidy when compared to fetuses without echogenic cardiac foci. The presence of an isolated intraventricular echogenic focus carried a relative risk of 4.08 compared to those fetuses in which ultrasonography had no finding associated with aneuploidy. In conclusion, these preliminary data indicate that presence of an intraventricular echogenic cardiac focus carries an increased risk of fetal aneuploidy.

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