SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints

Table 2 Known de novo pathogenic retrotransposon insertions associated with deletions ≥ 100 bp in the human genome

Gene	Chromosomal location	Disease	Retrotransposon (length)	Length of the deletion	Reference
HLA-A	6p22.1	Leukemia^a	SVA_F1 (2 kb)	~14 kb	[76]
ABCD1	Xq28	Adrenoleukodystrophy	AluYb9 (98 bp)	4,726 bp	[77]
SERPINC1	1q25.1	Antithrombin deficiency type 1	Alu (6 bp)^b	1,444 bp	[78]
LPL	8p21.3	Lipoprotein lipase deficiency	AluYb9 (150 bp)	2.2 kb	[79]
CHD7	8q12.2	CHARGE syndrome	AluYa5/8 (75 bp)	10 kb	[80]
PMM2	16p13.2	Congenital disorders of glycosylation type-Ia	AluYb8 (263 bp)	28 kb	[81]
APC	5q22.2	Familial adenomatous polyposis	AluYb9 (93 bp)	1,599 bp	[82]
EYA1	8q13.3	Branchio-oto-renal syndrome	L1 Hs (3,756 bp)	17 kb	[83]
PDHX	11p13	Pyruvate dehydrogenase complex deficiency	L1 Hs (6,086 bp)	46 kb	[84]
BRCA1	17q21.31	Hereditary breast/ovarian cancer	AluY (~190 bp)	23,363 bp	[85]

^aThe germline SVA insertion-associated deletion was identified in three unrelated Japanese families. Of the individuals harboring the SVA insertion-associated deletion, one individual in each family presented with leukemia.
^bThe affected family members harbored an intragenic 1,444 bp deletion and an insertion of a polyT tract of 40 nucleotides followed by a 6 bp sequence (5′-GAGACG-3′). This 6 bp sequence, located at the 3′end of the insertion, was homologous to the consensus sequence of the free right Alu monomer (FRAM).

ISSN: 1474-760X