Point-counterpoint. Patient autonomy and incidental findings in clinical genomics.

In spite of the centrality of informed consent in clinical genetics and genomics, new recommendations from the American College of Medical Genetics and Genomics (ACMG) call for laboratories and clinicians to test for and report specific genetic incidental findings, even when the patient does not consent to the testing or disclosure and even when the patient is a child.

Value of amniocentesis versus fetal tissue for cytogenetic analysis in cases of fetal demise.

Objective: Use of fetal tissue for cytogenetic analysis in cases of second- and third-trimester fetal demise frequently results in unacceptably high failure rates. We reviewed our ongoing use of amniocentesis prior to uterine evacuation to determine if this provided a better source of cells for cytogenetic analysis.

Methods: We compared cytogenetic results using fetal tissues obtained following uterine evacuation to our ongoing use of amniotic fluid cell obtained by transabdominal amniocentesis prior to uterine evacuation from 2003 to 2008.

The association between chorionic villus sampling and preeclampsia.

Objective: To determine whether an association exists between prenatal diagnostic procedures and preeclampsia.

Methods: All women who underwent invasive prenatal diagnosis and were not at high risk for preeclampsia were identified during a 15-month period and matched by age with women who had not had invasive prenatal diagnosis. The association between prenatal diagnosis [amniocentesis and chorionic villus sampling (CVS)] and the development of preeclampsia was assessed in univariable and multivariable analyses.

Culture of cells from maternal circulation, in conditions favoring fetal endothelial cell expansion, does not facilitate the preferential expansion of circulating fetal cells.

Objectives: To establish optimal culture conditions for fetal endothelial cells, and determine whether these can be used for preferential expansion of fetal cells from maternal blood.

Methods: Human adult microvascular and umbilical vein endothelial cells were cultured in the presence of colony-stimulating factor-1 (CSF-1), placental growth factor (PlGF), and transforming growth factor-beta1 (TGF-beta1). The effect of each cytokine was assessed.

The human gynome.

This year marks the 50th anniversary of the identification of the 3-dimensional structure of the DNA double helix and the completion of the US Human Genome Project. Now that we have completed the human genome sequence, what have we learned? How will this information benefit humankind? And, what are the implications for our patients in obstetrics and gynecology? Perhaps the biggest surprise is that there are only approximately 30,000 human genes, far fewer than earlier estimated. I propose the term "gynome" to describe that part of the human genome that is unique to women.

Culture of endothelial cells isolated from maternal blood using anti-CD105 and CD133.

Objectives: We hypothesized that fetal cells in maternal blood that do not respond to hematopoietic culture conditions represent endothelial cells. We investigated whether endothelial progenitor cells of fetal origin may be selected from maternal blood on the basis of their expression of CD133 or CD105 and expanded in culture.

Methods: Peripheral blood mononuclear cells from 16 pregnant women (gestational age: 11 to 24 weeks) were labeled with magnetic beads coupled to anti-CD133 or anti-CD105.

Interlaboratory comparison of fetal male DNA detection from common maternal plasma samples by real-time PCR.

Background: Analysis of fetal DNA from maternal plasma by PCR offers great potential for noninvasive prenatal genetic diagnosis. To further evaluate this potential, we developed and validated a standard protocol to determine whether fetal DNA sequences could be reproducibly amplified and measured across multiple laboratories in a common set of specimens.

Methods: Each of five participating centers in a National Institute of Child Health and Human Development consortium collected 20 mL of peripheral blood from 20 pregnant women between 10 and 20 weeks of gestation.

Intact fetal cells in maternal plasma: are they really there?

Rare fetal cells can be recovered from maternal blood, which suggests that non-invasive prenatal diagnosis is possible. However, recovery and analysis of fetal cells from blood is complex, and sensitivity is low because of the rarity of these cells in the maternal circulation. An alternative strategy, which suggested that intact fetal cells can be found in maternal plasma by use of simple enrichment methods, has been reported.

Culture of fetal cells from maternal blood for prenatal diagnosis.

The isolation and analysis of fetal cells from maternal blood would allow non-invasive prenatal genetic screening and diagnosis. Over the past decade, progress has been made towards this goal using various enrichment strategies and analysis by fluorescence in-situ hybridization with chromosome-specific probes and PCR. One method that is currently being explored involves culturing fetal cells.

Endothelial precursor cells in the peripheral blood of pregnant women.

Objective: To determine whether primitive endothelial precursor cells are present in the peripheral blood of pregnant compared with nonpregnant subjects and whether these precursor cells are of fetal or maternal origin.

Methods: Peripheral blood mononuclear cells from 13 pregnant women in the second trimester and from ten nonpregnant women and men were cultured for 8-10 weeks under conditions that promoted endothelial cell development. Early outgrowth (1 week culture) and late outgrowth (4-6 weeks) colonies were observed, their endothelial nature was investigated, and fluorescence in situ hybridization was performed to determine the origin of the colonies from pregnant women's specimens.

Evaluation of a culture system for enrichment of CD34+ hematopoietic progenitor cells present in maternal blood.

Background: Clonogenic expansion of fetal cells in maternal blood is one approach to overcome the very low number of target cells available for prenatal genetic analysis. However, efficient methods of enrichment, culturing conditions and subsequent analysis of fetal cells are lacking. Optimization of this technique requires more detailed evaluation of the composition and distribution of fetal cells that cross the placenta into the maternal circulation.

High-resolution two-dimensional electrophoretic survey of serum protein genetic types in Schmiedeleut Hutterites.

High-resolution, two-dimensional electrophoresis (2DE) was used to examine allele frequencies in eight serum protein marker systems and to screen for rare or previously undescribed alleles in 152 members of the Schmiedeleut branch of the Hutterite Brethren. The results include the first report of α -HS glycoprotein, apolipoprotein E, and SPPM-158 frequencies and haptoglobin 1F and 2S subtype frequencies in the Hutterites. Designed as part of ongoing genetic studies in this reproductively isolated population, this study was done to determine which markers might correlate with medical features or could be useful in population studies.