Characterizing partial AZFc deletions of the Y chromosome with amplicon-specific sequence markers.
BACKGROUND
The AZFc region of the human Y chromosome is a highly recombinogenic locus containing multi-copy male fertility genes located in repeated DNA blocks (amplicons). These AZFc gene families exhibit slight sequence variations between copies which are considered to have functional relevance. Yet, partial AZFc deletions yield phenotypes ranging from normospermia to azoospermia, thwarting definite conclusions on their real impact on fertility.


RESULTS
The amplicon content of partial AZFc deletion products was characterized with novel amplicon-specific sequence markers. Data indicate that partial AZFc deletions are a male infertility risk [odds ratio: 5.6 (95% CI: 1.6-30.1)] and although high diversity of partial deletion products and sequence conversion profiles were recorded, the AZFc marker profiles detected in fertile men were also observed in infertile men. Additionally, the assessment of rearrangement recurrence by Y-lineage analysis indicated that while partial AZFc deletions occurred in highly diverse samples, haplotype diversity was minimal in fertile men sharing identical marker profiles.


CONCLUSIONS
Although partial AZFc deletion products are highly heterogeneous in terms of amplicon content, this plasticity is not sufficient to account for the observed phenotypical variance. The lack of causative association between the deletion of specific gene copies and infertility suggests that AZFc gene content might be part of a multifactorial network, with Y-lineage evolution emerging as a possible phenotype modulator.
Navarro-Costa
Paulo
P
Centro de Genética Humana, Instituto Nacional de Saúde Dr, Ricardo Jorge, 1649-016 Lisboa, Portugal. navarro-costa@fm.ul.pt
Pereira
Luísa
L
Alves
Cíntia
C
Gusmão
Leonor
L
Proença
Carmen
C
Marques-Vidal
Pedro
P
Rocha
Tiago
T
Correia
Sónia C
SC
Jorge
Sónia
S
Neves
António
A
Soares
Ana P
AP
Nunes
Joaquim
J
Calhaz-Jorge
Carlos
C
Amorim
António
A
Plancha
Carlos E
CE
Gonçalves
João
J
D001483:Base Sequence; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D041322:Chromosomes, Human, Y; D005819:Genetic Markers; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D012307:Risk Factors
D005819:Genetic Markers