Recently, Professor Liang Xiaoyan's team from the Reproductive Medicine Center of the Sixth Affiliated Hospital of Sun Yat-sen University held a press conference to announce the world's first successful application of third-generation IVF technology to block the transmission of telomere fusion ring chromosomes to offspring. A healthy baby has now reached over a hundred days. This marks the first successful monoploid formation of telomere fusion ring chromosomes internationally, achieved through the improved long-read sequencing technology based on third-generation IVF sequencing.
The chromosomal karyotype result indicates the presence of a ring structure in one of the chromosomes, specifically chromosome 17. The subject, referred to as Xiaoxue (pseudonym), has a chromosomal abnormality with a ring-shaped chromosome, while the male partner has a gene mutation. Achieving a healthy pregnancy is extremely challenging for them. Ring chromosomes are a rare type of chromosomal structural abnormality in humans. Carriers generally have a lower fertility rate and are at risk of infertility, recurrent miscarriages, or giving birth to infants with abnormalities. Additionally, both Xiaoxue and her husband have de novo mutations, making it difficult to establish haplotypes from their parents' information, posing a challenge for embryo diagnosis.
To address the detection of ring chromosomes, the team led by Liang Xiaoyan developed a long-read sequencing method based on chained sequencing technology. Conventional second-generation sequencing typically has a read length of about 0.15 kb per end (the average length of telomeres at the ends of human chromosomes is 18-30 kb). Therefore, conventional second-generation sequencing cannot detect across telomere fusion regions. After technological improvements, the average read length in this case exceeded 30 kb, with relatively high base accuracy, enabling the detection of a large number of long DNA fragments spanning telomere fusion regions, thus confirming the structure of the ring chromosome.
Furthermore, through labeling, screening, and classification, the team successfully constructed haplotypes carrying the ring chromosome on chromosome 17 and normal chromosome haplotypes. They also successfully constructed haplotypes of the male partner's de novo pathogenic gene mutation. Subsequently, the team conducted integrated preimplantation genetic testing (PGT-plus) on embryos, successfully determining the presence of the ring chromosome and pathogenic gene mutations. Among 11 embryos, one embryo with both normal chromosomes and genes was successfully obtained.
It was reported that on December 7, 2023, the world's first "chromosome-delinked" baby was born successfully, and all related assessments and examinations were normal. Currently, Liang Xiaoyan's team has applied for a technical invention patent based on the technique of constructing haplotypes for such ring chromosomes. This technology is expected to be extended to other couples with chromosomal abnormalities and monogenic diseases.
"I hope this breakthrough research can bring hope to more families suffering from infertility and genetic disease risks, and also open up new avenues in the field of medicine," said Liang Xiaoyan.
