The genetic aspects of AAT deficiency and the variable manifestations of lung disease in PI Z individuals are reviewed. The role of modifying genetic factors which may interact with environmental factors (such as cigarette smoking) is discussed, and directions for future research are presented.

https://thorax.bmj.com/content/thoraxjnl/59/3/259.full.pdf

α1-Antitrypsin deficiency · 2: Genetic aspects of α1-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk

Comparative maps for mice and humans have been exceptionally important for predicting linkages, for identifying homologous mutations and disease loci, and for studying genome organization and evolution. This report summarizes the status of this comparative map. We provided a listing of homologous genes and anonymous loci that have been mapped in mice and humans together with references documenting homology and the chromosomal and linkage assignments (Table 1). We used a matrix to help readers find con-

/pdf/comparative-map-for-mice-and-humans-fygmq2ux5o.pdf

Comparative map for mice and humans.

Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantion

α1-antitrypsin deficiency is a genetic disorder which contributes to the development of chronic obstructive pulmonary disease, bronchiectasis, liver cirrhosis and panniculitis. The discovery of α1-ant

/pdf/alpha-one-antitrypsin-deficiency-from-gene-to-treatment-13il4ih3ie.pdf

Alpha one antitrypsin deficiency: from gene to treatment.

The human protease inhibitor genes α1 antitrypsin (α1-PI) and α1-antichymotrypsin (α1-ACT) are acute-phase proteins which are induced in response to inflammation. These inhibitors function to limit the activity of serine proteases in vivo. α1-PI acts as an inhibitor of neutrophil elastase to protect the elastin fibers of the lung. Genetic deficiencies of α1-PI result in development of chronic pulmonary emphysema. The physiologic role of α1-ACT has not been clearly defined, but it also appears to function in the maintenance of protease-protease inhibitor equilibrium in the lung. Nucleic acid and protein sequence homologies detected between α1-PI and α1 t-ACT suggested an evolutionary relationship. Gene mapping experiments were performed to determine if these protease inhibitor genes reside at the same chromosomal locus in man. In situ hybridization data demonstrate that both α1-PI and α1-ACT map to the same region, q31–q32.3, on chromosome 14.

Regional location of α1-antichymotrypsin and α1-antitrypsin genes on human chromosome 14

alpha 1-Antitrypsin is a major plasma protease inhibitor synthesized in the liver. Genetic deficiency of this protein predisposes the affected individuals to development of infantile liver cirrhosis or chronic obstructive pulmonary emphysema. The human chromosomal alpha 1-antitrypsin gene has been cloned and shown to contain three introns in the peptide-coding region. When the cloned alpha 1-antitrypsin gene was used as a hybridization probe to analyze Eco RI-digested genomic DNA from different individuals, two distinct bands of 9.6 kilobases (kb) and 8.5 kb in length were observed in every case. Further analysis using only labeled intronic DNA as the hybridization probe has indicated that the authentic alpha 1-antitrypsin gene resides within the 9.6-kb fragment. Thus the 8.5-kb fragment must contain another gene that is closely related in sequence to the alpha 1-antitrypsin gene. Using a series of human-Chinese hamster somatic cell hybrids containing unique combinations of human chromosomes, the alpha 1-antitrypsin gene as well as the sequence-related gene have been assigned to human chromosome 14 by Southern hybridization and synteny analysis.

E C Lai

Papers

Assignment of the alpha 1-antitrypsin gene and a sequence-related gene to human chromosome 14 by molecular hybridization