PGT應用於偵測罕見聽力喪失遺傳疾病(HHL)

PGT採用方法有傳統PCR, FISH, array comparative genomic hybridization (aCGH), single-nucleotide polymorphism (SNP) arrays, next-generation sequencing (目前主流為NGS)

1. PCR容易汙染造成假陽性或陰性 同時偵測標的受限無法應付多基因造成之遺傳疾病
2. FISH缺點為偵測標的受限 無法偵測所有染色體基因變異
3. aCGH缺點為偵測prob受限 無法偵測所有染色體基因變異
4. SNP & NGS可偵測所有基因組genome   SNP 陣列依賴於探針的全基因組分佈。但範圍過於廣泛
5. NGS 可以檢測各種遺傳變異，從單核苷酸變異到更大的結構變異，提供全面的遺傳訊息
6. 本篇採用low coverage NGS 兼具偵測足夠廣泛, 偵測效率&精確
7. 由於罕見基因疾病病患人數稀少 目前針對罕見疾病之PGT nGS應用發表稀少

Clinical application of preimplantation genetic testing based on low-coverage next-generation sequencing with linkage analyses in hereditary hearing loss families

• PGT can be offered for more than 1700 monogenic disorders. 
• The embryo genotypes were diagnosed by low-coverage sequencing combined with SNP linkage analysis.
• The 19 couples include variants of autosomal recessive hearing loss gene GJB2, SLC26A4, USH2A, CDH23, and autosomal dominant hearing loss gene MITF, WFS1, and GSDME. 
• PGT based on low-coverage next-generation sequencing with linkage analyses can block the transmission of deafness-related mutations to offspring. 2–3 × depth of embryo sequencing data enabled a credible testing of 205 deafness-related mutations loci. 
• 
  

Pathogenic genes	19 (100.00)
GJB2	5(26.32)
SLC26A4	7 (36.84)
USH2A	2 (10.53)
CDH23	1 (5.26)
MITF	1 (5.26)
WFS1	1 (5.26)
GSDME	1 (5.26)
GJB2 + SLC26A4	1 (5.26)

• PCR  is highly susceptible to contamination, which can lead to false positives or false negatives. 
• FISH cannot cover all human chromosomes and has a higher error rate. 
• aCGH enables genome-wide detection, but its resolution and diagnostic capabilities are restricted by the fixed number of probes. 
• SNP-array relies on the genome-wide distribution of probes. 
• NGS can detect a wide range of genetic variations, from single nucleotide changes to larger structural variants, offering comprehensive genetic information.