A review of pre-implantation genetic testing technologies and applications

The first practice of pre-implantation genetic testing(PGT)was reported more than 30 years ago.PGT,originally named preimplantation genetic screening(PGS)and pre-implantation genetic diagnosis(PGD),is now categorized as PGT for aneuploidies(PGT-A),PGT for monogenic/single-gene defects(PGT-M),and PGT for chromosomal structural rearrangements(PGT-SR).Patients with fertility issues caused by advanced maternal age,carrier status of chromosomal abnormalities,or harboring pathogenic variant(s)are recommended to undergo PGT to increase the possibility of successful live birth and avoid potentially affected newborns.High-throughput techniques,such as DNA microarrays and next-generation sequencing(NGS),have enabled comprehensive screening of all 24 chromosomes,instead of few loci at a time.Furthermore,as a comprehensive PGT,PGT-Plus was enabled by the rapid development of a genome-wide single-cell haplotyping technique to detect embryo aneuploidy,single-gene disorders,and chromosomal aberrations simultaneously using a single universal protocol.In addition,non-invasive approaches enable a more intact embryo during the biopsy procedure,which may avoid potential mosaicism issues at a certain scale by testing spent culture media(SCM).As a novel PGT application,PGT-P detects genome-wide variations in polygenic diseases,which account for a large proportion of premature human deaths and affect a markedly larger population than monogenic diseases,using polygenic risk score calculation to decrease the potential of affecting complex conditions.Owing to the emergence of new technologies recruited to PGTs,more couples with infertility issues have a promising chance of conceiving a healthy baby,ultimately facilitating the human species to live more prosper.

Newborn screening with targeted sequencing:a multicenter investigation and a pilot clinical study in China

Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.