Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding.

Abstract

Data on structural chromosome abnormalities identified during prenatal diagnosis were used to estimate the number of such abnormalities that would be detectable in an unselected series of newborns using moderate levels of banding (400 to 500 bands). These estimates were compared with the rates detected in nonbanded surveys of newborns.Between 1976 and 1990 prenatal diagnosis using banding techniques was carried out in our laboratory on 14677 women aged 35 and over. Among these, we detected 112 structural rearrangements, 32 unbalanced and 80 balanced. These figures were adjusted by two methods to give an estimate of the frequency of structural abnormalities in the newborn. Our data suggest that the use of moderate levels of banding increases the frequency of unbalanced structural abnormalities from 0-052 to 0-061% and of balanced structural abnormalities from 0-212 to 0-522%. Thus, the total number of chromosome abnormalities detectable in the newborn is increased from 0-60% in unbanded preparations to 0-92% in banded preparations.

Fertility, reproductive outcomes, and health of offspring, of patients treated for Hodgkin's disease: an investigation including chromosome examinations

“…We found no chromosome abnormalities attributable to the treated parent However, chromosome analysis will not detect subtle changes to the DNA, including conventional mutations. In the general population almost 1% of individuals have a chromosome abnormality when similar levels of banding are used (Jacobs et al, 1992). Our findings enable us to rule out at the 95% level of confidence that more than 8% of offspring in the study group overall would have had abnormalities, and larger percentages for subgroups of the data.…”

Homozygosity for constitutional chromosomal rearrangements: a systematic review with reference to origin, ascertainment and phenotype

“…In the majority of cases, both parents were heterozygous for the specific translocation and each contributed to the subsequent homozygous offspring. In most instances (cases [1][2][3][4][5]8), there was a consanguinous parental relationship with a familial translocation. These include three siblings (cases 1-3) each heterozygous for t (13;14).…”

“…1 Data suggest that such rearrangements are present in B0.6-1% of individuals, with reported differences dependant on the population studied (for example unselected newborns or selected prenatal or population studies) and the level of banding techniques used. [2][3][4][5][6] Additional considerations include the proportion of balanced versus unbalanced abnormalities and origin of the rearrangement; that is whether inherited or de novo. The relative prevalence and the underlying mutations rate vary for each category of rearrangement and for specific types within each category.…”

“…15 Approximately 90% of all non-homologous RBTs and reciprocal translocations are balanced, with the estimated prevalence of balanced chromosomal inversions even higher. 3,8,[16][17][18] Studies suggest that the majority of constitutional rearrangements are inherited; B60% of non-homologous RBTs; between 65 and 75% of reciprocal translocations and over 90% of inversions. 2,8,[16][17][18] Although the familial transmission of such rearrangements across generations is well reported, reports of homozygosity are relatively rare, although include examples of all three forms.…”

Cytogenetics and gene discovery in psychiatric disorders

“…The reason for this rarity becomes clear when the factors involved are considered: the prevalence and the number of genes that can give rise to the disorder, the frequency of chromosome abnormalities in the population, the size of the human genome, the size of the gene loci themselves and the efficiency of clinical ascertainment. Assuming an average gene size of 27 kb, 9 a genome size of 3 billion bases, two breakpoints per chromosome abnormality (eg a typical reciprocal translocation/inversion) and a frequency of such abnormalities in the population of 0.29-0.56% 10,11 then, providing the disruption is compatible with life, any given gene would be cytogenetically disrupted in 3-6 individuals in the UK population of B60 million. However, for any specific locus this is probably an underestimate because breakpoints are unlikely to occur as a truly random phenomenon.…”