Page 141 - PCC11

MOLECULAR GENETIC TESTS: GWAS
TO DETECT MALE/ FEMALE INFERTILITY (POI)
FEMALE INFERTILITY POI
Kang 2008
Knauff 2009
Qin 2012
Pyun 2012
Oldenburg 2008
Caburet 2012
Ethnicity
Korean
Caucasian (Dutch)
Chinese
Korean
Dutch
Middle‐Eastern
Discovery set
# cases
24
99
391
24
10
5
#controls
24
181
895
24
5
4
Associations
PTHB1 7p14
Ht1 – GAAAG POI susceptible
HtII – TGTGC POI resistant
ADAMTS19 intron
88q22.3 (10‐6)
22 SNPs in LAMC1
5q14.1‐q15
7p21.1‐15.3 7q21.3‐22.2
Replication set
# cases
101
60
400
98
‐
‐
#controls
87
90
800
218
‐
‐
Results
PTHB1
Ht1 – POI susceptible
No confirmation
9 SNPs & 1Ht
‐
DXL5, DXL6, DSS1 seq no causal mutation
Page 135 of 155
The ABC of next generation sequencing-based genetic diagnostics in fertility
8-6-2018 | 17
MOLECULAR GENETIC TESTS: LOCUS-SPECIFIC < > GENOME-WIDE
TO DETECT MALE/ FEMALE I NFERTI LI TY
All DNA-variants in exons of a gene
locus-specific
1 gene gene panel all genes
genome GWAS
All DNA-variants in exons of gene package simultaneous
Targeted (small)
‘All’ coding sequences of human genome (>180,000 exons), sequenced & analysed in 1 experiment
Exome (all DNA-variants in exons of a genome)
± 1 % of complete human genome
Targeted (large)
all mendelian genes
Mendeliome (all DNA-variants in exons of mendelian genes)
Targeted (medium)
Complete genome (all DNA-variants in genome)
genome-wide
‘SNPs in genome’ (frequent DNA-variants in genome)
targeted
The ABC of next generation sequencing-based genetic diagnostics in fertility
8-6-2018 | 18
PRECONGRESS COURSE 11 I BARCELONA, SPAIN – 1 JULY 2018 141