Copy Neutral Changes Identified by Single - Nucleotide Polymorphism (SNP) Microarray Analysis during Prenatal Diagnosis

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American Journal of Obstetrics and Gynecology







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Objective To assess the clinical impact of copy neutral changes detected by single-nucleotide polymorphism (SNP) microarray analysis during prenatal diagnosis. Study Design A retrospective review was performed on amniotic fluid specimens from one prenatal diagnosis center and patients with copy neutral changes were identified on SNP microarray analysis. Clinical impacts including further testing options and patient decisions were evaluated. Results Twelve cases with isolated copy neutral changes were identified among a total of 443 amniotic fluid specimens (2.7%) sent for SNP microarray analysis. There were four cases with an increased number of short contiguous runs of regions of homozygosity (ROH) associated with an isolated population, two cases of long ROH in chromosomes 7 and 14 suggesting possible uniparental disomy (UPD), and six cases with long stretches of ROH in multiple chromosomes indicating identity by descent. Four of the cases had further analysis performed through an online ROH analysis tool in an attempt to identify recessive genes in the ROH region that were associated with specific ultrasound findings seen in the fetuses and positive results were seen in two cases. Two genes associated with cleft lip were identified in one case and one gene associated with clubfeet was found in the other case. In both cases, further genetic testing options were offered and the patients declined to proceed. UPD was ruled out in the case with possible UPD 14 and the patient declined UPD testing on the case with a possible UPD 7. After being informed of the microarray results and the significance of the ROH findings, all patients opted to continue with the pregnancy except one, who terminated due to severe abnormal ultrasounds findings and poor prognosis of the fetus. Of the pregnancies continued, one patient had a fetal demise at 22 weeks and another patient was induced at 29 weeks due to holoprosencephaly. Conclusion Copy neutral changes were seen in 2.7% of patients in our study. The identification of these changes provided more testing options for the patients and helped patients make better informed decisions. Due to the complexity of these findings, genetic counseling is important. Detection of copy neutral changes did not seem to change pregnancy decisions in our small patient population. Previous research suggested that the chemical composition of rock varnish, a micrometer thick Si/AI/Mn/Fe coating, changed predictably through time and so could be used as a chronometer. In particular, the cation ratio, (Ca+K)/Ti, was posited to decrease as the varnish aged. However, many earlier varnish studies were not well documented and were based on chemical analyses now shown to be inaccurate. This paper describes a test and the first direct comparison between two different analytic methods used previously to “cation-ratio date” archeologic and geologic materials. It provides methodology sufficiently detailed for replication of analytical and sampling techniques. Our analyses of rock varnish from a prehistoric chert quarry in California show that the two principal methods used to “cation-ratio date” rock varnish generate consistently different elemental abundances and are therefore not comparable. Neither analytic method produced a significant time-dependent trend in varnish chemistry, suggesting rock varnish cation ratios are not a reproducible and thus probably not a reliable way to date lithic artifacts.


Obstetrics and Gynecology



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