As the molecular basis for an increasing number of genetic disorders is determined, many conditions that were not previously detectable prenatally by other means can now be diagnosed by analyzing fetal DNA. Any technique used for direct variant analysis can be used for prenatal diagnosis on a fetal DNA sample extracted from amniotic fluid or CVS samples or from cell cultures derived from these samples. Three main modalities that can be used are single- gene testing, either by sequencing or targeted analysis for a known variant, gene panel sequencing, or sequencing of the exome or genome. Because not 100% of the exome (all exons) or genome (all genomic DNA) can be sequenced, we refer to these as exome sequencing (ES) and genome sequencing rather than whole exome or whole genome sequencing.

Single- Gene Testing and Gene Panel Sequencing for Prenatal Diagnosis

When there is a known familial pathogenic variant for which the fetus is at risk, or a recognizable fetal condition, such as thanatophoric dysplasia, a lethal skeletal dysplasia caused by only a few different pathogenic variants, a specific targeted molecular test can be done to determine if that variant is detected in the fetal DNA. These tests are highly accurate, but such clinical presentations are relatively rare. More commonly, fetal anomalies detected by ultrasonography are suggestive for a class of genetic disorders. In those situations, a gene panel sequencing test, which analyzes a variable number of genes that have been associated with that class of disorders (e.g., a broad skeletal dysplasia panel), can be done. These panels have limitations. They are usually designed based on gene- disease relationships that are recognized postnatally, but the prenatal phenotypes for the same conditions may not be well known or may differ from those observed postnatally. In addition, the gene content of these panels needs to be kept up to date with the rapidly growing knowledge of gene- disease relationships. Participation of medical geneticists or genetic counselors, whose role it is to stay informed about these rapid changes, is essential for counseling and selection of such tests for prenatal diagnosis. This type of genetic testing is reserved for pregnancies found to be at increased risk and not for routine screening or testing.

Exome Sequencing and Genome Sequencing for Prenatal Diagnosis

In addition to the above mentioned limitations of gene panels for sequencing of DNA from fetuses diagnosed with congenital anomalies, it is increasingly recognized that the genetic basis for many fetal anomalies, in particular those that lead to fetal or neonatal demise, are not yet known. Furthermore, some prenatally diagnosed fetal anomalies may be caused by variants in genes known to cause a different phenotype postnatally, which is referred to as prenatal phenotype expansion. For these reasons and because of its success in diagnosing genetic conditions postnatally, multiple studies have investigated the benefit of prenatal ES of fetal DNA for pregnancies complicated with fetal anomalies for which standard testing by CMA has not yielded a diagnosis. A few large studies have demonstrated that in these circumstances the diagnostic rate is between 8.5% and 13%, but in some more selected series that include pregnancies with stronger suspicion for a single gene disorder, it is higher, ranging from ~20% to 40%, or up to 80% in very selected series with fetal skeletal dysplasias. Much more research is needed on the impact of prenatal exome sequencing on the care of pregnancies and newborns, but professional societies are now sup porting its clinical use for selected pregnancies when a diagnosis cannot otherwise be made. This test should be offered by genetics providers who are familiar with prenatal genetics and the complexities of such testing and who are skilled at counseling pregnant individuals and their partners about its benefits and limitations. With exome sequencing there is a substantially higher chance of detecting unwanted findings such as VUS, incidental and secondary findings, including possible diagnosis of adult- onset disorders, and unexpected paternity. The analysis of exome sequences is more complex and time consuming, and it may take longer to obtain results than for prenatal CMA and karyotypes. To speed up variant interpretation, prenatal exome sequencing is primarily done in trios, where the parental DNAs are also sequenced and analyzed to help interpret the variants found in the fetal DNA.

More recently, trio genome sequencing is also being studied for prenatal diagnosis. While it is more comprehensive, evaluating both noncoding and coding regions of DNA as well as including the possibility of copy number analysis, the information obtained from genome sequencing is even more complex. Prenatal genome sequencing is a rapidly evolving area that bears watching closely in the years ahead, with increasingly important ethical and policy implications for the practice of fetal medicine and prenatal genetics.

اخر الاخبار

اخبار العتبة العباسية المقدسة

جناح العتبة العباسية المقدسة في معرض طهران الدولي يشهد فعاليات متنوِّعة

شعبة مدارس الكفيل تطلق حملتها السنوية لدعم العوائل المتعففة في شهر رمضان المبارك

بأجواء رمضانية مميزة.. مجموعة مشاتل الكفيل تستقبل العوائل العراقية يوميًا

المجمع العلمي: الختمة القرآنية الرمضانية المركزية المرتلة تشهد تنوعًا في القراءات والمشاركات

المزيد

الآخبار الصحية

دراسة تكشف "السبب الخفي" وراء ترك التمارين الرياضية

كشف التوقيت "المثالي" لتغيير فرشاة الأسنان

بلاستيك في أنسجة بشرية.. دراسة تكشف مفاجأة طبية

دراسة تحذر من الإفراط في ممارسة الرياضة.. كيف يضر دماءك؟

المزيد

الآخبار التكنلوجية

"ديب سيك" تحجب أحدث نماذجها عن شركات الرقائق الأميركية

"سامسونغ" تطلق سلسلة هواتف "غالاكسي إس 26"

حملات سرية ورسائل تشويه.. كيف يتم استغلال "تشات جي بي تي"؟

أثر نفسي غير متوقع للرياضة.. مرتبط بالغضب

المزيد

مواضيع ذات صلة

Globin Gene Clusters

Molecular Analysis of Nucleic Acid Sequences

Genes and Genome Complexity

Structure of Nucleic Acids

Genomics: Genome-Wide Analysis of Gene Structure and Function

Chromosomal Organization of Genes and Noncoding DNA

RNA Interference Causes Gene Inactivation by Destroying the Corresponding mRNA

Linkage Studies Can Map Disease Genes with a Resolution of About 1 Centimorgan

DNA Polymorphisms Are Used as Markers for Linkage Mapping of Human Mutations

The Two- Hit Theory of Tumor Suppressor Gene Inactivation in Cancer

DNA Microarrays Can Be Used to Evaluate the Expression of Many Genes at One Time

Hybridization Techniques Permit Detection of Specific DNA Fragments and mRNAs