Page 89 - ESHRE2019
P. 89
‘Single-gene’ vs. Complex diseases
Single-gene (‘Mendelian’)
• Caused by single, rare, variants that carry a very high risk
• Disease primarily identified in families
• Examples: Cystic fibrosis; Huntingdon’s disease
• Typical study design: Family-based Studies
Complex
• Caused by multiple genetic variants + environmental factors, each
carrying small increases in risk
• Disease observed in families as well as sporadic cases
• Examples: Cancers, CVD, Type I/II Diabetes, Endometriosis.......
• Typical study design: Genome-wide Association Studies (GWAS)
NB Sub-types of complex diseases can be monogenic,
Example: Familial breast and ovarian cancer caused by BRCA1/2 mutations.....
Is there a single-gene subtype of endometriosis? Large-scale analyses based on families (2005/2007)
Breast cancer
Endometriosis
214 breast cancer families:
BRCA1 - Maximum LOD Score = 21.68... Accounts for 60-70% of all familial breast
cancer
1,176 affected sister-pairs:
Maximum LOD Score = 3.09 248 families with 3+ cases:
Maximum LOD score = 3.52
The existence of a single high-risk gene accounting for most of familial endometriosis cases in the population is very unlikely....
84
PRECONGRESS COURSE 03 I VIENNA, AUSTRIA – 23 JUNE 2019 87
