To select embryos free of single-nucleotide defects or chromosomal abnormalities following in vitro fertilization (IVF) and during preimplantation genetic diagnosis and screening, researchers combine targeted or whole-genome amplification methods with linkage analysis. However, the approach often involves performing multiple procedures on the same embryos, posing safety risks.
Now, researchers developed a next-generation DNA sequencing-based method called mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) to simultaneously identify disease-related point mutations and chromosomal defects and perform linkage analysis on biopsies of 5-day-old human IVF embryos.
Using MARSALA, the authors screened embryos from two couples: one in which the 32-year-old father was afflicted with a hereditary bone disorder caused by a point mutation, and the other in which the 33-year-old mother carried a mutant recessive allele for an X-linked disorder marked by hair, teeth, and sweat gland defects.
One embryo per couple was implanted and carried to term, resulting in the birth of two healthy baby girls free of the parental mutations, as confirmed by prenatal analysis of amniotic fluid cells and postnatal DNA sequencing of umbilical cord blood cells.
According to the authors, MARSALA might represent a precise and cost-effective method for preimplantation diagnosis and screening of IVF embryos for single-gene and chromosomal defects in autosomes and sex chromosomes.